We now describe another series ( B ) of such variants , which differ from A series cells grown in similar concentrations of 1 , 25D3 in that they express the CD14 antigen and nonspecific esterase , characteristic of the monocyte , while continuing to proliferate and they develop hypotetraploid DNA ( 4C ) content at higher concentrations of ambient 1 , 25D3 than the A series cells .

We now describe another series ( B ) of such variants , which differ from A series cells grown in similar concentrations of 1 , 25D3 in that they express the <protein>CD14 antigen</protein> and nonspecific <protein>esterase</protein> , characteristic of the monocyte , while continuing to proliferate and they develop hypotetraploid DNA ( 4C ) content at higher concentrations of ambient 1 , 25D3 than the A series cells .


Cells in the B series with 4C DNA content ( 100B and 200B ) also differed from the A series 4C cells by the absence of DNA binding by the full-length Sp1 transcription factor .

Cells in the B series with 4C DNA content ( 100B and 200B ) also differed from the <cell_line>A series 4C cells</cell_line> by the absence of DNA binding by the full-length <protein>Sp1</protein> <protein>transcription factor</protein> .


However , B series cells resembled the A series cells in exhibiting faster growth rates than the parental HL60 cells and showed high levels of vitamin D receptor and retinoid receptor X proteins .

However , B series cells resembled the A series cells in exhibiting faster growth rates than the parental <cell_line>HL60 cells</cell_line> and showed high levels of <protein>vitamin D receptor</protein> and <protein>retinoid receptor X proteins</protein> .


These results show that the initial steps in the 1 , 25D3 signaling pathway are intact in B series resistant cells and lead to the appearance of early markers of monocytic differentiation .


However , the progression to subsequent events which comprise terminal differentiation and cell cycle arrest is halted during the adaptation to the presence of 1 , 25D3 in these cells .


Thus , the availability of these variant cells should provide a system for studying the link between differentiation and cell cycle arrest .


Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists .

Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of <protein>anti-Tat single-chain intrabodies</protein> and NF-kappa B antagonists .


Human immunodeficiency virus type 1 ( HIV-1 ) Tat , an early regulatory protein that is critical for viral gene expression and replication , transactivates the HIV-1 long terminal repeat ( LTR ) via its binding to the transactivation response element ( TAR ) and , along with other cellular factors , increases viral transcription initiation and elongation .

<protein>Human immunodeficiency virus type 1 ( HIV-1 ) Tat</protein> , an early <protein>regulatory protein</protein> that is critical for viral gene expression and replication , transactivates the <dna>HIV-1 long terminal repeat</dna> ( <dna>LTR</dna> ) via its binding to the <dna>transactivation response element</dna> ( <dna>TAR</dna> ) and , along with other cellular factors , increases viral transcription initiation and elongation .


Tat also superactivates the HIV-1 promoter through a TAR -independent mechanism , including tumor necrosis factor alpha-induced and protein kinase C ( PKC ) -dependent activation of NF-kappa B , and inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat -mediated LTR superactivation .

Tat also superactivates the <dna>HIV-1 promoter</dna> through a <dna>TAR</dna> -independent mechanism , including tumor necrosis factor alpha-induced and protein kinase C ( <protein>PKC</protein> ) -dependent activation of <protein>NF-kappa B</protein> , and inhibitors of <protein>Tat</protein> and <protein>NF-kappa B</protein> cooperatively down-regulate this <protein>Tat</protein> -mediated <dna>LTR</dna> superactivation .


In this study , a combined pharmacologic and genetic strategy using two PKC ( NF-kappa B ) inhibitors , pentoxifylline ( PTX ) and Go-6976 , and a stably expressed anti-Tat single-chain intracellular antibody ( sFv intrabody ) was employed to obtain cooperative inhibition of both HIV-1 LTR -driven gene expression and HIV-1 replication .

In this study , a combined pharmacologic and genetic strategy using two <protein>PKC</protein> ( <protein>NF-kappa B</protein> ) inhibitors , pentoxifylline ( PTX ) and Go-6976 , and a stably expressed <protein>anti-Tat single-chain intracellular antibody</protein> ( <protein>sFv intrabody</protein> ) was employed to obtain cooperative inhibition of both HIV-1 <dna>LTR</dna> -driven gene expression and HIV-1 replication .


Treatment of cells with PTX and Go-6976 resulted in cooperative inhibition of both HIV-1 LTR -driven gene expression and HIV-1 replication .

Treatment of cells with PTX and Go-6976 resulted in cooperative inhibition of both <dna>HIV-1 LTR</dna> -driven gene expression and HIV-1 replication .


In addition , the combined use of anti-Tat sFv intrabodies and the two NF-kappa B inhibitors retained the virus in the latent state for as long as 45 days .

In addition , the combined use of <protein>anti-Tat sFv intrabodies</protein> and the two <protein>NF-kappa B</protein> inhibitors retained the virus in the latent state for as long as 45 days .


The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the NF-kappa B inhibitors alone or the anti- Tat sFv intrabodies alone .

The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the <protein>NF-kappa B</protein> inhibitors alone or the anti- <protein>Tat sFv intrabodies</protein> alone .


Together , these results suggest that in future clinical gene therapy trials , a combined pharmacologic and genetic strategy like the one reported here may improve the survival of transduced cells and prolong clinical benefit .

Together , these results suggest that in future clinical gene therapy trials , a combined pharmacologic and genetic strategy like the one reported here may improve the survival of <cell_line>transduced cells</cell_line> and prolong clinical benefit .


Transcription factors in immune-mediated disease .

<protein>Transcription factors</protein> in immune-mediated disease .


A large amount of detailed information about the intracellular proteins regulating NF-kappa B activation and the cellular response to NF-kappa B activation has emerged recently .

A large amount of detailed information about the <protein>intracellular proteins</protein> regulating <protein>NF-kappa B</protein> activation and the cellular response to <protein>NF-kappa B</protein> activation has emerged recently .


Several small molecules , an antisense oligonucleotide , and gene therapeutic agents that inhibit NF-kappa b activation have been described .

Several small molecules , an <dna>antisense oligonucleotide</dna> , and gene therapeutic agents that inhibit <protein>NF-kappa b</protein> activation have been described .


Despite this , there are still significant gaps in our understanding of this process and its consequences .


In contrast , the characterization of transcription factors selectively regulating cytokine production by CD4+ T cell subsets is at a very early stage .

In contrast , the characterization of <protein>transcription factors</protein> selectively regulating cytokine production by <cell_type>CD4+ T cell subsets</cell_type> is at a very early stage .


Three interacting proteins have recently been shown to contribute to subset-restricted expression of the IL-4 gene .

Three <protein>interacting proteins</protein> have recently been shown to contribute to subset-restricted expression of the <dna>IL-4 gene</dna> .


There are other elements regulating IL-4 gene expression , however , and the relative importance of these recently identified proteins has yet to be determined .

There are other elements regulating <dna>IL-4 gene</dna> expression , however , and the relative importance of these recently identified proteins has yet to be determined .


Involvement of Rel , Fos , and Jun proteins in binding activity to the IL-2 promoter CD28 response element/AP-1 sequence in human T cells .

Involvement of <protein>Rel , Fos , and Jun proteins</protein> in binding activity to the <dna>IL-2 promoter CD28 response element/AP-1 sequence</dna> in <cell_type>human T cells</cell_type> .


CD28 is an important costimulatory molecule in the activation of human T cells .

<protein>CD28</protein> is an important <protein>costimulatory molecule</protein> in the activation of <cell_type>human T cells</cell_type> .


Costimulation of T cells through both the Ag receptor and CD28 leads to high level IL-2 production , which is vital to the development of an immune response in vivo .

Costimulation of <cell_type>T cells</cell_type> through both the Ag receptor and <protein>CD28</protein> leads to high level <protein>IL-2</protein> production , which is vital to the development of an immune response in vivo .


Previous reports have suggested the CD28 stimulation contributes to the activation of the IL-2 promoter by up-regulating the activity of several transcription factors , including AP-1 and nuclear factor-kappaB ( NF-kappaB ) /Rel family members as well as an uncharacterized transcription factor called CD28 response complex .

Previous reports have suggested the <protein>CD28</protein> stimulation contributes to the activation of the <dna>IL-2 promoter</dna> by up-regulating the activity of several <protein>transcription factors</protein> , including <protein>AP-1</protein> and <protein>nuclear factor-kappaB ( NF-kappaB ) /Rel family members</protein> as well as an <protein>uncharacterized transcription factor</protein> called <protein>CD28</protein> response complex .


While several lines of investigation have suggested that NF-kappaB/Rel family members make up the CD28 response complex transcription factor , other work has not supported this conclusion .

While several lines of investigation have suggested that <protein>NF-kappaB/Rel family members</protein> make up the <protein>CD28</protein> response complex <protein>transcription factor</protein> , other work has not supported this conclusion .


Recent studies suggest that the CD28 response element ( CD28RE ) does not function independently but works instead in conjunction with the adjacent promoter proximal AP-1-binding site and this hypothesis is confirmed here .

Recent studies suggest that the <dna>CD28 response element</dna> ( <dna>CD28RE</dna> ) does not function independently but works instead in conjunction with the <dna>adjacent promoter proximal AP-1-binding site</dna> and this hypothesis is confirmed here .


Also in the current study , binding activity to the CD28RE/AP-1 sequence of the IL-2 promoter is evaluated .

Also in the current study , binding activity to the <dna>CD28RE/AP-1 sequence</dna> of the <dna>IL-2 promoter</dna> is evaluated .


Although four specific complexes can be detected binding to this sequence , only one of these complexes is specific for both the CD28RE and the adjacent AP-1 site .

Although four specific complexes can be detected binding to this sequence , only one of these complexes is specific for both the <dna>CD28RE</dna> and the <dna>adjacent AP-1 site</dna> .


Of the NF-kappaB/Rel family members tested , this CD28RE/AP-1-specific complex contains predominantly c-Rel , despite the fact that both p50 and RelA can efficiently bind to the CD28RE .

Of the <protein>NF-kappaB/Rel family members</protein> tested , this <protein>CD28RE/AP-1-specific complex</protein> contains predominantly <protein>c-Rel</protein> , despite the fact that both <protein>p50</protein> and <protein>RelA</protein> can efficiently bind to the <dna>CD28RE</dna> .


c-Fos and c-Jun are also found in this CD28RE/AP-1-specific complex .

<protein>c-Fos</protein> and <protein>c-Jun</protein> are also found in this <protein>CD28RE/AP-1-specific complex</protein> .


These data indicate that functional complexes encompassing both the CD28RE and the AP-1-binding sites influence IL-2 promoter activity in CD28 -costimulated T cells .

These data indicate that functional complexes encompassing both the <dna>CD28RE</dna> and the <dna>AP-1-binding sites</dna> influence <dna>IL-2 promoter</dna> activity in <protein>CD28</protein> -costimulated <cell_type>T cells</cell_type> .


Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells [ see comments ]

Inducible expression and phosphorylation of <protein>coactivator BOB.1/OBF.1</protein> in <cell_type>T cells</cell_type> [ see comments ]


BOB.1/OBF.1 is a transcriptional coactivator that is constitutively expressed in B cells and interacts with the Oct1 and Oct2 transcription factors .

<protein>BOB.1/OBF.1</protein> is a <protein>transcriptional coactivator</protein> that is constitutively expressed in <cell_type>B cells</cell_type> and interacts with the Oct1 and Oct2 <protein>transcription factors</protein> .


Upon activation of Jurkat T cells and primary murine thymocytes with phorbol esters and ionomycin , BOB.1/OBF.1 expression and transactivation function were induced .

Upon activation of <cell_line>Jurkat T cells</cell_line> and <cell_type>primary murine thymocytes</cell_type> with phorbol esters and ionomycin , <protein>BOB.1/OBF.1</protein> expression and transactivation function were induced .


BOB.1/OBF.1 was phosphorylated at Ser184 both in vivo and in vitro , and this modification was required for inducible activation .

<protein>BOB.1/OBF.1</protein> was phosphorylated at Ser184 both in vivo and in vitro , and this modification was required for inducible activation .


Mutation of Ser184 also diminished transactivation function in B cells , suggesting that the activating phosphorylation that is inducible in T cells is constitutively present in B cells .

Mutation of Ser184 also diminished transactivation function in <cell_type>B cells</cell_type> , suggesting that the activating phosphorylation that is inducible in <cell_type>T cells</cell_type> is constitutively present in <cell_type>B cells</cell_type> .


Thus , BOB.1/OBF.1 is a transcriptional coactivator that is critically regulated by posttranslational modifications to mediate cell type-specific gene expression .

Thus , <protein>BOB.1/OBF.1</protein> is a <protein>transcriptional coactivator</protein> that is critically regulated by posttranslational modifications to mediate cell type-specific gene expression .


Increased expression of Gs ( alpha ) enhances activation of the adenylyl cyclase signal transduction cascade .

Increased expression of <protein>Gs ( alpha )</protein> enhances activation of the <protein>adenylyl cyclase</protein> signal transduction cascade .


Expression of the stimulatory G protein , G ( S ) alpha , can vary over a 3-fold range in human tissues and in rodent central nervous system .

Expression of the stimulatory <protein>G protein</protein> , <protein>G ( S ) alpha</protein> , can vary over a 3-fold range in human tissues and in rodent central nervous system .


In fact , the offspring of alcoholics have higher levels of G ( S ) alpha expression in certain tissues compared with the offspring of nonalcoholics .

In fact , the offspring of alcoholics have higher levels of <protein>G ( S ) alpha</protein> expression in certain tissues compared with the offspring of nonalcoholics .


The aim of this research was to test the hypothesis that a causal relationship exists between the level of expression of G ( S ) alpha and induction of the adenylyl cyclase ( AC ) cascade .

The aim of this research was to test the hypothesis that a causal relationship exists between the level of expression of <protein>G ( S ) alpha</protein> and induction of the <protein>adenylyl cyclase</protein> ( AC ) cascade .


The methodology employed transient transfection of HEK 293 cells with a cDNA for the 52-kDa form of G ( S ) alpha under regulation by inducible metallothionein promoters .

The methodology employed transient transfection of <cell_line>HEK 293 cells</cell_line> with a cDNA for the 52-kDa form of <protein>G ( S ) alpha</protein> under regulation by <dna>inducible metallothionein promoters</dna> .


Transfectants were exposed to varying concentrations ( 0-125 microM ) of zinc sulfate that produced a 3-fold range of membrane G ( S ) alpha expression .

Transfectants were exposed to varying concentrations ( 0-125 microM ) of zinc sulfate that produced a 3-fold range of membrane <protein>G ( S ) alpha</protein> expression .


The range of G ( S ) alpha expression produced was found to mimic a physiologically relevant spectrum of G ( S ) alpha expression in membranes derived from human tissues and rat brain .

The range of <protein>G ( S ) alpha</protein> expression produced was found to mimic a physiologically relevant spectrum of <protein>G ( S ) alpha</protein> expression in membranes derived from human tissues and rat brain .


It was observed that induction of G ( S ) alpha expression increased constitutive as well as stimulated cAMP accumulation .

It was observed that induction of <protein>G ( S ) alpha</protein> expression increased constitutive as well as stimulated cAMP accumulation .


Moreover , induction of G ( S ) alpha expression increased events distal to the accumulation of cAMP including the phosphorylation of the transcription factor , cAMP response element binding protein and transcriptional activation of cAMP-dependent reporter genes .

Moreover , induction of <protein>G ( S ) alpha</protein> expression increased events distal to the accumulation of cAMP including the phosphorylation of the transcription factor , <protein>cAMP response element binding protein</protein> and transcriptional activation of <dna>cAMP-dependent reporter genes</dna> .


In summary , these studies show that the amount of G ( S ) alpha expression has a marked impact on the level of activity of the AC cascade from the membrane through to the nucleus .

In summary , these studies show that the amount of <protein>G ( S ) alpha</protein> expression has a marked impact on the level of activity of the AC cascade from the membrane through to the nucleus .


It is hypothesized that individuals who differ in G ( S ) alpha expression may also differ in the expression of certain cAMP-dependent genes .

It is hypothesized that individuals who differ in <protein>G ( S ) alpha</protein> expression may also differ in the expression of certain <dna>cAMP-dependent genes</dna> .


Thrombin generation by apoptotic vascular smooth muscle cells .

<protein>Thrombin</protein> generation by <cell_type>apoptotic vascular smooth muscle cells</cell_type> .


Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface , classically provided by activated platelets .

<protein>Thrombin</protein> activation requires assembly of a <protein>prothrombinase complex</protein> of activated <protein>coagulation factors</protein> on an anionic phospholipid surface , classically provided by <cell_type>activated platelets</cell_type> .


We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells ( VSMCs ) undergoing apoptosis after serum withdrawal .

We have previously shown that anionic phosphatidylserine is exposed by <cell_type>rat vascular smooth muscle cells</cell_type> ( <cell_type>VSMCs</cell_type> ) undergoing apoptosis after serum withdrawal .


In this study , using a chromogenic assay , we have shown thrombin generation by apoptotic VSMCs expressing c-myc ( VSMC-myc ) with an area under the thrombin -generation curve ( AUC ) of 305 +/- 17 nmol x min/L and a peak thrombin ( PT ) of 154 +/- 9 nmol/L .

In this study , using a chromogenic assay , we have shown <protein>thrombin</protein> generation by <cell_type>apoptotic VSMCs</cell_type> expressing <protein>c-myc</protein> ( <cell_line>VSMC-myc</cell_line> ) with an area under the <protein>thrombin</protein> -generation curve ( AUC ) of 305 +/- 17 nmol x min/L and a peak <protein>thrombin</protein> ( PT ) of 154 +/- 9 nmol/L .


The thrombin -generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets ( P = .003 for AUC ; P = .0002 for PT ) and similar to calcium-ionophore activated platelets ( AUC of 332 +/- 15 nmol x min/L , P = .3 ; PT of 172 +/- 8 nmol/L , P = .2 ) .

The <protein>thrombin</protein> -generating potential of the <cell_line>apoptotic VSMC-myc cells</cell_line> was greater than that of <cell_type>unactivated platelets</cell_type> ( P = .003 for AUC ; P = .0002 for PT ) and similar to calcium-ionophore <cell_type>activated platelets</cell_type> ( AUC of 332 +/- 15 nmol x min/L , P = .3 ; PT of 172 +/- 8 nmol/L , P = .2 ) .


Thrombin activation was also seen with apoptotic human VSMCs ( AUC of 211 +/- 8 nmol x min/L ; PT of 103 +/- 4 nmol/L ) and was inhibited by annexin V ( P < .0001 for AUC and PT ) .

<protein>Thrombin</protein> activation was also seen with <cell_type>apoptotic human VSMCs</cell_type> ( AUC of 211 +/- 8 nmol x min/L ; PT of 103 +/- 4 nmol/L ) and was inhibited by annexin V ( P < .0001 for AUC and PT ) .


VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal ( P = .0002 for AUC and PT ) .

<cell_line>VSMC-myc cells</cell_line> maintained in serum generated less <protein>thrombin</protein> than after serum withdrawal ( P = .0002 for AUC and PT ) .


VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin ( AUC of 260 +/- 2 nmol x min/L ; PT of 128 +/- 4 nmol/L ) .

<cell_type>VSMCs</cell_type> derived from human coronary atherosclerotic plaques that apoptose even in serum also generated <protein>thrombin</protein> ( AUC of 260 +/- 2 nmol x min/L ; PT of 128 +/- 4 nmol/L ) .


We conclude that apoptotic VSMCs possess a significant thrombin -generating capacity secondary to phosphatidylserine exposure .

We conclude that <cell_type>apoptotic VSMCs</cell_type> possess a significant <protein>thrombin</protein> -generating capacity secondary to phosphatidylserine exposure .


Apoptotic cells within atherosclerotic plaques may allow local thrombin activation , thereby contributing to disease progression .

Apoptotic cells within atherosclerotic plaques may allow local <protein>thrombin</protein> activation , thereby contributing to disease progression .


An isotype-specific activator of major histocompatibility complex ( MHC ) class II genes that is independent of class II transactivator .

An isotype-specific activator of <dna>major histocompatibility complex ( MHC ) class II genes</dna> that is independent of <protein>class II transactivator</protein> .


Patients with one type of major histocompatibility complex class II combined immunodeficiency have mutations in a gene termed class II transactivator ( CIITA ) , which coordinately controls the transcription of the three major human class II genes , HLA-DR , -DQ , and -DP .

Patients with one type of <protein>major histocompatibility complex class II</protein> combined immunodeficiency have mutations in a gene termed <protein>class II transactivator</protein> ( <protein>CIITA</protein> ) , which coordinately controls the transcription of the three major <dna>human class II genes</dna> , <dna>HLA-DR , -DQ , and -DP</dna> .


However , the experimentally derived B-lymphoblastoid cell line , clone 13 , expresses high levels of HLADQ in the absence of HLA-DR and HLA-DP , despite its mapping by complementation analysis to this group .

However , the experimentally derived <cell_line>B-lymphoblastoid cell line</cell_line> , <cell_line>clone 13</cell_line> , expresses high levels of <protein>HLADQ</protein> in the absence of <dna>HLA-DR</dna> and <dna>HLA-DP</dna> , despite its mapping by complementation analysis to this group .


It was possible that one of the clone 13 CIITA alleles bore a mutation that allowed HLA-DQ , but not HLA-DR or -DP transcription .

It was possible that one of the <dna>clone 13 CIITA alleles</dna> bore a mutation that allowed <dna>HLA-DQ</dna> , but not HLA-DR or -DP transcription .


Alternatively , another factor , distinct from CIITA , might control HLA-DQ expression .

Alternatively , another factor , distinct from <protein>CIITA</protein> , might control <dna>HLA-DQ</dna> expression .


We report here that ectopic expression of CIITA cDNAs derived by reverse transcriptase polymerase chain reaction from clone 13 do not restore expression of HLA-DQ in another CIITA-deficient cell line , RJ2.2.5 .

We report here that ectopic expression of <dna>CIITA cDNAs</dna> derived by reverse transcriptase polymerase chain reaction from <cell_line>clone 13</cell_line> do not restore expression of <dna>HLA-DQ</dna> in another <cell_line>CIITA-deficient cell line</cell_line> , <cell_line>RJ2.2.5</cell_line> .


In addition , no CIITA protein is detectable in clone 13 nuclear extracts .

In addition , no <protein>CIITA</protein> protein is detectable in <cell_line>clone 13</cell_line> nuclear extracts .


In contrast , somatic cell fusion between clone 13 and RJ2.2.5 restored expression of the HLA-DQ haplotype encoded by the RJ2.2.5 DQB gene .

In contrast , somatic cell fusion between <cell_line>clone 13</cell_line> and <cell_line>RJ2.2.5</cell_line> restored expression of the <dna>HLA-DQ</dna> haplotype encoded by the <dna>RJ2.2.5 DQB gene</dna> .


Taken together , these data demonstrate the existence of an HLA-DQ isotype-specific trans-acting factor , which functions independently of CIITA .

Taken together , these data demonstrate the existence of an <protein>HLA-DQ isotype-specific trans-acting factor</protein> , which functions independently of <protein>CIITA</protein> .


Homodimerization of the human interleukin 4 receptor alpha chain induces Cepsilon germline transcripts in B cells in the absence of the interleukin 2 receptor gamma chain .

Homodimerization of the <protein>human interleukin 4 receptor alpha chain</protein> induces <rna>Cepsilon germline transcripts</rna> in <cell_type>B cells</cell_type> in the absence of the <protein>interleukin 2 receptor gamma chain</protein> .


The cytokines interleukin ( IL ) -4 and IL-13 play a critical role in inducing Cepsilon germline transcripts and IgE isotype switching in human B cells .

The <protein>cytokines</protein> <protein>interleukin ( IL ) -4</protein> and <protein>IL-13</protein> play a critical role in inducing <rna>Cepsilon germline transcripts</rna> and <protein>IgE isotype</protein> switching in <cell_type>human B cells</cell_type> .


The IL-4 receptor ( IL-4R ) in B cells is composed of two chains , the IL-4-binding IL-4Ralpha chain , which is shared with the IL-13R , and the IL-2Rgamma ( gammac ) chain , which is shared with IL-7R , IL-9R , and IL-15R .

The <protein>IL-4 receptor</protein> ( <protein>IL-4R</protein> ) in <cell_type>B cells</cell_type> is composed of two chains , the <protein>IL-4-binding IL-4Ralpha chain</protein> , which is shared with the <protein>IL-13R</protein> , and the <protein>IL-2Rgamma ( gammac ) chain</protein> , which is shared with <protein>IL-7R</protein> , <protein>IL-9R</protein> , and <protein>IL-15R</protein> .


IL-4 induces Cepsilon germline transcripts and IgE isotype switching in B cells from patients with gammac chain deficiency .

<protein>IL-4</protein> induces <rna>Cepsilon germline transcripts</rna> and <protein>IgE isotype</protein> switching in <cell_type>B cells</cell_type> from patients with <protein>gammac chain</protein> deficiency .


Induction of Cepsilon germline transcripts by IL-4 in B cells that lack the gammac chain may involve signaling via the IL-13R .

Induction of <rna>Cepsilon germline transcripts</rna> by <protein>IL-4</protein> in <cell_type>B cells</cell_type> that lack the <protein>gammac chain</protein> may involve signaling via the <protein>IL-13R</protein> .


Alternatively , the IL-4Ralpha chain may transduce intracellular signals that lead to Cepsilon gene transcription independently of its association with other chains .

Alternatively , the <protein>IL-4Ralpha chain</protein> may transduce intracellular signals that lead to <dna>Cepsilon gene</dna> transcription independently of its association with other chains .


We show that ligand-induced homodimerization of chimeric surface receptors consisting of the extracellular and transmembrane domains of the erythropoietin receptor and of the intracellular domain of IL-4Ralpha induces Janus kinase 1 ( Jak1 ) activation , STAT6 activation , and Cepsilon germline transcripts in human B cell line BJAB .

We show that ligand-induced homodimerization of <protein>chimeric surface receptors</protein> consisting of the <protein>extracellular and transmembrane domains</protein> of the <protein>erythropoietin receptor</protein> and of the <protein>intracellular domain</protein> of <protein>IL-4Ralpha</protein> induces <protein>Janus kinase 1</protein> ( <protein>Jak1</protein> ) activation , <protein>STAT6</protein> activation , and <rna>Cepsilon germline transcripts</rna> in <cell_line>human B cell line BJAB</cell_line> .


Disruption of the Jak1-binding proline-rich Box1 region of IL-4Ralpha abolished signaling by this chimeric receptor .

Disruption of the <protein>Jak1-binding proline-rich Box1 region</protein> of <protein>IL-4Ralpha</protein> abolished signaling by this <protein>chimeric receptor</protein> .


Furthermore , B cells transfected with a chimeric CD8alpha/IL-4Ralpha receptor , which is expressed on the cell surface as a homodimer , constitutively expressed Cepsilon germline transcripts .

Furthermore , <cell_type>B cells</cell_type> transfected with a <protein>chimeric CD8alpha/IL-4Ralpha receptor</protein> , which is expressed on the cell surface as a <protein>homodimer</protein> , constitutively expressed <rna>Cepsilon germline transcripts</rna> .


These results suggest that homodimerization of the IL-4Ralpha chain is sufficient to transduce Jak1 -dependent intracellular signals that lead to IgE isotype switching .

These results suggest that homodimerization of the <protein>IL-4Ralpha chain</protein> is sufficient to transduce <protein>Jak1</protein> -dependent intracellular signals that lead to <protein>IgE isotype</protein> switching .


Transcriptional activity and constitutive nuclear localization of the ETS protein Elf-1 .

Transcriptional activity and constitutive nuclear localization of the <protein>ETS protein</protein> <protein>Elf-1</protein> .


Elf-1 is a lymphoid-specific transcription factor that belongs to the ETS protein family .

<protein>Elf-1</protein> is a <protein>lymphoid-specific transcription factor</protein> that belongs to the <protein>ETS protein family</protein> .


It can bind to DNA target sequences within a variety of cytokine genes .

It can bind to DNA target sequences within a variety of <dna>cytokine genes</dna> .


We demonstrate that Elf-1 is constitutively localized in the nucleus which is dependent on the presence of amino acids 86-265 .

We demonstrate that <protein>Elf-1</protein> is constitutively localized in the nucleus which is dependent on the presence of <protein>amino acids 86-265</protein> .


Analysis of Gal4-Elf-1 fusion proteins revealed that the N-terminal 86 amino acids of Elf-1 contain a transcriptional activation domain , the activity of which is attenuated by an internal repression domain .

Analysis of <protein>Gal4-Elf-1 fusion proteins</protein> revealed that the N-terminal 86 amino acids of <protein>Elf-1</protein> contain a <protein>transcriptional activation domain</protein> , the activity of which is attenuated by an <protein>internal repression domain</protein> .


Furthermore , Elf-1 interacts specifically with the E74 target sequence and can stimulate transcription driven by the E74 site independent of mitogenic signaling .

Furthermore , <protein>Elf-1</protein> interacts specifically with the <dna>E74 target sequence</dna> and can stimulate transcription driven by the <dna>E74 site</dna> independent of mitogenic signaling .


Thus , Elf-1 is able to stimulate gene transcription which may be required for the development and activity of lymphocytes .

Thus , <protein>Elf-1</protein> is able to stimulate gene transcription which may be required for the development and activity of <cell_type>lymphocytes</cell_type> .


Characterization of peripheral blood T-lymphocytes transduced with HTLV-I Tax mutants with different trans-activating phenotypes .

Characterization of <cell_type>peripheral blood T-lymphocytes</cell_type> transduced with <protein>HTLV-I Tax mutants</protein> with different trans-activating phenotypes .


Tax1 , a transcriptional trans-activator of the Human T-cell leukemia virus type I ( HTLV-I ) , induces the expression of many cellular genes through interaction with at least three distinct cellular transcription factors ; CREB/ATF , NF-kappaB , and SRF .

<protein>Tax1</protein> , a <protein>transcriptional trans-activator</protein> of the Human T-cell leukemia virus type I ( HTLV-I ) , induces the expression of many cellular genes through interaction with at least three distinct <protein>cellular transcription factors</protein> ; <protein>CREB/ATF</protein> , <protein>NF-kappaB</protein> , and <protein>SRF</protein> .


This Tax1 -induced activation of cellular genes is considered to be a critical event in T-cell transformation by HTLV-I .

This <protein>Tax1</protein> -induced activation of <dna>cellular genes</dna> is considered to be a critical event in T-cell transformation by HTLV-I .


To elucidate the role of each Tax1 -inducible transcriptional pathway in T-cell transformation , we introduced Tax1 mutants with different trans-activating phenotypes into peripheral blood lymphocytes ( PBL ) by retroviral vectors .

To elucidate the role of each <protein>Tax1</protein> -inducible transcriptional pathway in T-cell transformation , we introduced <protein>Tax1 mutants</protein> with different trans-activating phenotypes into <cell_type>peripheral blood lymphocytes</cell_type> ( <cell_type>PBL</cell_type> ) by retroviral vectors .


Analysis of these PBLs revealed that activation of the NF-kappaB pathway is sufficient to promote the growth response to IL-2 .

Analysis of these <cell_type>PBLs</cell_type> revealed that activation of the <protein>NF-kappaB</protein> pathway is sufficient to promote the growth response to <protein>IL-2</protein> .


However , for the clonal expansion of CD4+ T-cells , which is a characteristic result of HTLV-I infection , activation of the CREB/ATF and SRF pathways is also required .

However , for the clonal expansion of <cell_type>CD4+ T-cells</cell_type> , which is a characteristic result of HTLV-I infection , activation of the CREB/ATF and SRF pathways is also required .


Epstein-Barr virus binding to CD21 activates the initial viral promoter via NF-kappaB induction .

Epstein-Barr virus binding to <protein>CD21</protein> activates the initial <dna>viral promoter</dna> via <protein>NF-kappaB</protein> induction .


Epstein-Barr virus ( EBV ) , an oncogenic human herpesvirus , binds to and infects normal human B lymphocytes via CD21 , the CR2 complement receptor .

Epstein-Barr virus ( EBV ) , an oncogenic human herpesvirus , binds to and infects <cell_type>normal human B lymphocytes</cell_type> via <protein>CD21</protein> , the <protein>CR2 complement receptor</protein> .


Studies of the mechanisms that enable EBV to infect nonactivated , noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor , which , in turn , binds to and mediates transcriptional activation of Wp , the initial viral latent gene promoter .

Studies of the mechanisms that enable EBV to infect nonactivated , <cell_type>noncycling B cells</cell_type> provide compelling evidence for a sequence of events in which EBV binding to <protein>CD21</protein> on purified <cell_type>resting human B cells</cell_type> rapidly activates the <protein>NF-kappaB</protein> <protein>transcription factor</protein> , which , in turn , binds to and mediates transcriptional activation of Wp , the initial <dna>viral latent gene promoter</dna> .


Thus , EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB -dependent intracellular signaling pathway which is required for infection .

Thus , EBV binding to its cellular receptor on resting B cells triggers an <protein>NF-kappaB</protein> -dependent intracellular signaling pathway which is required for infection .


Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo .

Synthetic glucocorticoids that dissociate transactivation and <protein>AP-1</protein> transrepression exhibit antiinflammatory activity in vivo .


Some of the most potent antiinflammatory and immunosuppressive agents are synthetic glucocorticoids .


However , major side effects severely limit their therapeutic use .


The development of improved glucocorticoid-based drugs will require the separation of beneficial from deleterious effects .


One possibility toward this goal is to try to dissociate two main activities of glucocorticoids , i.e. transactivation and transrepression .


Screening of a library of compounds using transactivation and AP-1 transrepression models in transiently transfected cells identified dissociated glucocorticoids , which exert strong AP-1 inhibition but little or no transactivation .

Screening of a library of compounds using transactivation and <protein>AP-1</protein> transrepression models in transiently transfected cells identified dissociated glucocorticoids , which exert strong <protein>AP-1</protein> inhibition but little or no transactivation .


Importantly , despite high ligand binding affinity , the prototypic dissociated compound , RU24858 , acted as a weak agonist and did not efficiently antagonize dexamethasone-induced transcription in transfected cells .

Importantly , despite high ligand binding affinity , the prototypic dissociated compound , RU24858 , acted as a weak agonist and did not efficiently antagonize dexamethasone-induced transcription in <cell_type>transfected cells</cell_type> .


Similar results were obtained in hepatic HTC cells for the transactivation of the endogenous tyrosine amino transferase gene ( TAT ) , which encodes one of the enzymes involved in the glucocorticoid-dependent stimulation of neoglucogenesis .

Similar results were obtained in <cell_line>hepatic HTC cells</cell_line> for the transactivation of the <dna>endogenous tyrosine amino transferase gene</dna> ( <dna>TAT</dna> ) , which encodes one of the enzymes involved in the glucocorticoid-dependent stimulation of neoglucogenesis .


To investigate whether dissociated glucocorticoids retained the antiinflammatory and immunosuppressive potential of classic glucocorticoids , several in vitro and in vivo models were used .


Indeed , secretion of the proinflammatory lymphokine interleukin-1beta was severely inhibited by dissociated glucocorticoids in human monocytic THP 1 cells .

Indeed , secretion of the <protein>proinflammatory lymphokine interleukin-1beta</protein> was severely inhibited by dissociated glucocorticoids in <cell_line>human monocytic THP 1 cells</cell_line> .


Moreover , in two in vivo models , these compounds exerted an antiinflammatory and immunosuppressive activity as potent as that of the classic glucocorticoid prednisolone .


These results may lead to an improvement of antiinflammatory and immunosuppressive therapies and provide a novel concept for drug discovery .


In vivo footprinting and mutational analysis of the proximal CD19 promoter reveal important roles for an SP1/Egr-1 binding site and a novel site termed the PyG box .

In vivo footprinting and mutational analysis of the <dna>proximal CD19 promoter</dna> reveal important roles for an <dna>SP1/Egr-1 binding site</dna> and a novel site termed the <dna>PyG box</dna> .


CD19 expression begins at the pro-B cell stage of B cell development .

<protein>CD19</protein> expression begins at the pro-B cell stage of B cell development .


As such it serves as a good prototype for B cell-specific genes whose expression begins shortly after lineage commitment .

As such it serves as a good prototype for <dna>B cell-specific genes</dna> whose expression begins shortly after lineage commitment .


To understand the molecular mechanisms controlling CD19 gene expression , we isolated and functionally characterized the CD19 promoter using in vivo footprinting , gel shift assays , and transfection studies .

To understand the molecular mechanisms controlling <protein>CD19</protein> gene expression , we isolated and functionally characterized the <dna>CD19 promoter</dna> using in vivo footprinting , gel shift assays , and transfection studies .


Reporter constructs spanning portions of the promoter identified a region between -85 and -200 that produced high levels of reporter gene activity in lymphoid cells .

Reporter constructs spanning portions of the promoter identified a <dna>region between -85 and -200</dna> that produced high levels of reporter gene activity in <cell_type>lymphoid cells</cell_type> .


In vivo footprinting identified protected regions over the known high affinity B cell lineage-specific activator protein ( BSAP ) site , the low affinity BSAP site , a SP1/Egr-1 site termed the CD19 GC box , and two novel sites named the AT box and PyG box .

In vivo footprinting identified protected regions over the known high affinity <dna>B cell lineage-specific activator protein ( BSAP ) site</dna> , the <dna>low affinity BSAP site</dna> , a <dna>SP1/Egr-1 site</dna> termed the <dna>CD19 GC box</dna> , and two novel sites named the <dna>AT box</dna> and <dna>PyG box</dna> .


Phorbol ester treatment of a pre-B cell line up-regulated CD19 expression , induced Egr-1 , and enhanced the footprint over the GC box .

Phorbol ester treatment of a <cell_line>pre-B cell line</cell_line> up-regulated <protein>CD19</protein> expression , induced <protein>Egr-1</protein> , and enhanced the footprint over the GC box .


Gel shift assays demonstrated SP1 and Egr-1 binding to the CD19 GC box , while unknown nuclear proteins bound the PyG and AT boxes .

Gel shift assays demonstrated SP1 and <protein>Egr-1</protein> binding to the <dna>CD19 GC box</dna> , while unknown nuclear proteins bound the <dna>PyG and AT boxes</dna> .


Mutations in the AT box or in the BSAP sites did not affect CD19 reporter construct activity , while a mutation of the GC box reduced it modestly , and a PyG box mutation reduced it dramatically .

Mutations in the <dna>AT box</dna> or in the <dna>BSAP sites</dna> did not affect <protein>CD19</protein> <dna>reporter construct</dna> activity , while a mutation of the <dna>GC box</dna> reduced it modestly , and a <dna>PyG box</dna> mutation reduced it dramatically .


BSAP failed to trans-activate CD19 promoter constructs in B cells or non-B cells , suggesting that cis elements such as the PyG and GC boxes are also necessary for high level CD19 promoter expression .

<protein>BSAP</protein> failed to trans-activate <dna>CD19 promoter constructs</dna> in <cell_type>B cells</cell_type> or <cell_type>non-B cells</cell_type> , suggesting that cis elements such as the <dna>PyG and GC boxes</dna> are also necessary for high level <dna>CD19 promoter</dna> expression .


EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes .

<protein>EBF</protein> and <protein>E47</protein> collaborate to induce expression of the <dna>endogenous immunoglobulin surrogate light chain genes</dna> .


Early B cell factor ( EBF ) and E47 participate in the transcriptional control of early B lymphocyte differentiation .

<protein>Early B cell factor</protein> ( <protein>EBF</protein> ) and <protein>E47</protein> participate in the transcriptional control of early B lymphocyte differentiation .


With the aim of identifying genetic targets for these transcription factors , we stably transfected cDNAs encoding EBF or a covalent homodimer of E47 , individually or together , into immature hematopoietic Ba/F3 cells , which lack both factors .

With the aim of identifying genetic targets for these transcription factors , we stably <dna>transfected cDNAs</dna> encoding <protein>EBF</protein> or a covalent homodimer of <protein>E47</protein> , individually or together , into <cell_line>immature hematopoietic Ba/F3 cells</cell_line> , which lack both factors .


In combination , EBF and E47 induce efficient expression of the endogenous immunoglobulin surrogate light chain genes , lambda5 and VpreB , whereas other pre-B cell-specific genes remain silent .

In combination , <protein>EBF</protein> and <protein>E47</protein> induce efficient expression of the <dna>endogenous immunoglobulin surrogate light chain genes</dna> , <dna>lambda5</dna> and <dna>VpreB</dna> , whereas other <dna>pre-B cell-specific genes</dna> remain silent .


Multiple functionally important EBF and E47 binding sites were identified in the lambda5 promoter/enhancer region , indicating that lambda5 is a direct genetic target for these transcription factors .

Multiple functionally important <dna>EBF and E47 binding sites</dna> were identified in the <dna>lambda5 promoter/enhancer region</dna> , indicating that <dna>lambda5</dna> is a direct genetic target for these <protein>transcription factors</protein> .


Taken together , these data suggest that EBF and E47 synergize to activate expression of a subset of genes that define an early stage of the B cell lineage .

Taken together , these data suggest that <protein>EBF</protein> and <protein>E47</protein> synergize to activate expression of a subset of genes that define an early stage of the <cell_type>B cell lineage</cell_type> .


Cytokines : shared receptors , distinct functions .

<protein>Cytokines</protein> : shared <protein>receptors</protein> , distinct functions .


That the signal transduction pathways used by the cytokines IL-2 and IL-15 are identical would suggest that these cytokines have redundant roles in lymphoid development ; instead , IL-2 is the guardian of thymus-derived T-cell homeostasis , while interleukin-15 promotes extrathymic development of T and NK cells .

That the signal transduction pathways used by the <protein>cytokines</protein> <protein>IL-2</protein> and <protein>IL-15</protein> are identical would suggest that these <protein>cytokines</protein> have redundant roles in lymphoid development ; instead , <protein>IL-2</protein> is the guardian of thymus-derived T-cell homeostasis , while <protein>interleukin-15</protein> promotes extrathymic development of <cell_type>T and NK cells</cell_type> .


The IL-4 receptor alpha-chain cytoplasmic domain is sufficient for activation of JAK-1 and STAT6 and the induction of IL-4 -specific gene expression .

The <protein>IL-4 receptor alpha-chain cytoplasmic domain</protein> is sufficient for activation of <protein>JAK-1</protein> and <protein>STAT6</protein> and the induction of <protein>IL-4</protein> -specific gene expression .


The common gamma-chain ( gamma ( c ) ) is a functional component of the IL-4R , yet cells lacking gamma ( c ) are able to respond to IL-4 .

The <protein>common gamma-chain</protein> ( <protein>gamma ( c )</protein> ) is a functional component of the <protein>IL-4R</protein> , yet cells lacking <protein>gamma ( c )</protein> are able to respond to <protein>IL-4</protein> .


This has led to the suggestion that a surrogate gamma'-chain , which can interact with the IL-4R alpha chain to mediate signaling , is expressed on cells lacking gamma ( c ) .

This has led to the suggestion that a <protein>surrogate gamma'-chain</protein> , which can interact with the <protein>IL-4R alpha chain</protein> to mediate signaling , is expressed on cells lacking <protein>gamma ( c )</protein> .


An alternative possibility is that in the absence of gamma ( c ) , the IL-4R alpha chain is able to transduce signals by homodimerization .

An alternative possibility is that in the absence of <protein>gamma ( c )</protein> , the <protein>IL-4R alpha chain</protein> is able to transduce signals by homodimerization .


To test this latter possibility , a chimeric receptor containing the extracellular domain of c-kit ( the stem cell factor ( SCF ) receptor ) and the cytoplasmic and transmembrane domains of the IL-4R alpha chain was generated .

To test this latter possibility , a <protein>chimeric receptor</protein> containing the <protein>extracellular domain</protein> of <protein>c-kit</protein> ( the <protein>stem cell factor ( SCF ) receptor</protein> ) and the <protein>cytoplasmic and transmembrane domains</protein> of the <protein>IL-4R alpha chain</protein> was generated .


Treatment of cells expressing the chimeric receptor kit/IL-4R alpha with SCF induces activation of the IL-4R alpha-associated kinase JAK-1 and the transcription factor STAT6 .

Treatment of cells expressing the <protein>chimeric receptor</protein> <protein>kit/IL-4R alpha</protein> with <protein>SCF</protein> induces activation of the <protein>IL-4R alpha-associated kinase</protein> <protein>JAK-1</protein> and the <protein>transcription factor</protein> <protein>STAT6</protein> .


However , tyrosine phosphorylation of JAK-3 , which associates with gamma ( c ) , is not induced by SCF in these cells .

However , tyrosine phosphorylation of <protein>JAK-3</protein> , which associates with <protein>gamma ( c )</protein> , is not induced by <protein>SCF</protein> in these cells .


SCF -mediated ligation of kit/IL-4R alpha is sufficient to elicit IL-4 -specific gene expression , including up-regulation of CD23 and synthesis of germ-line epsilon transcripts .

<protein>SCF</protein> -mediated ligation of <protein>kit/IL-4R alpha</protein> is sufficient to elicit <protein>IL-4</protein> -specific gene expression , including up-regulation of <protein>CD23</protein> and synthesis of <rna>germ-line epsilon transcripts</rna> .


In the T cell line CTLL2 , ligation of kit/IL-4R alpha induces cellular proliferation .

In the <cell_line>T cell line CTLL2</cell_line> , ligation of <protein>kit/IL-4R alpha</protein> induces cellular proliferation .


Finally , in JAK-1-deficient HeLa cells , STAT6 activation by IL-4 is completely abolished .

Finally , in <cell_line>JAK-1-deficient HeLa cells</cell_line> , <protein>STAT6</protein> activation by <protein>IL-4</protein> is completely abolished .


Together , these data demonstrate that the IL-4R alpha cytoplasmic domain is sufficient to activate JAK-1 and STAT6 and to induce expression of IL-4 target genes , thus identifying a mechanism by which IL-4 signaling can proceed in the absence of JAK-3 and gamma ( c ) .

Together , these data demonstrate that the <protein>IL-4R alpha cytoplasmic domain</protein> is sufficient to activate <protein>JAK-1</protein> and <protein>STAT6</protein> and to induce expression of <dna>IL-4 target genes</dna> , thus identifying a mechanism by which <protein>IL-4</protein> signaling can proceed in the absence of <protein>JAK-3</protein> and <protein>gamma ( c )</protein> .


Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937 .

Histamine modulates the expression of <dna>c-fos</dna> through cyclic AMP production via the <protein>H2 receptor</protein> in the <cell_line>human promonocytic cell line U937</cell_line> .


We examined the effects of histamine and its agonists on the expression of the c-fos and c-myc proto-oncogenes at the transcriptional and translational levels in the human promonocytic U937 cell line .

We examined the effects of histamine and its agonists on the expression of the <dna>c-fos and c-myc proto-oncogenes</dna> at the transcriptional and translational levels in the <cell_line>human promonocytic U937 cell line</cell_line> .


Histamine transiently increased cAMP and c-fos expression through H2 receptors .

Histamine transiently increased cAMP and <dna>c-fos</dna> expression through <protein>H2 receptors</protein> .


Dibutyryl cAMP also increased c-fos mRNA and protein , and levels remained elevated even after 12 hr of treatment .

Dibutyryl cAMP also increased <rna>c-fos mRNA</rna> and <protein>protein</protein> , and levels remained elevated even after 12 hr of treatment .


Dose-dependence studies using histamine and dimaprit showed that the EC50 values for cAMP production and c-fos increase were similar , suggesting that cAMP might be involved in c-fos induction via H2 receptors .

Dose-dependence studies using histamine and dimaprit showed that the EC50 values for cAMP production and <dna>c-fos</dna> increase were similar , suggesting that cAMP might be involved in <dna>c-fos</dna> induction via <protein>H2 receptors</protein> .


Furthermore , studies carried out using H7 , a protein kinase A/protein kinase C inhibitor , blocked c-fos induction , whereas no effect was observed with bisindolylmaleimide , a specific protein kinase C inhibitor .

Furthermore , studies carried out using <protein>H7</protein> , a <protein>protein kinase A/protein kinase C inhibitor</protein> , blocked <dna>c-fos</dna> induction , whereas no effect was observed with bisindolylmaleimide , a specific <protein>protein kinase C</protein> inhibitor .


No modification of c-myc expression could be detected on treatment with histamine or its analogues .

No modification of <dna>c-myc</dna> expression could be detected on treatment with histamine or its analogues .


Nevertheless , dibutyryl cAMP induced a down-regulation of the levels of this proto-oncogene .

Nevertheless , dibutyryl cAMP induced a down-regulation of the levels of this <dna>proto-oncogene</dna> .


In addition , dibutyryl cAMP inhibited cell growth in a dose-dependent manner , whereas histamine failed to affect proliferation and differentiation of U937 cells .

In addition , dibutyryl cAMP inhibited cell growth in a dose-dependent manner , whereas histamine failed to affect proliferation and differentiation of <cell_line>U937 cells</cell_line> .


Cells pretreated with dimaprit showed a decrease in the cAMP response to subsequent addition of H2 agonists , whereas the cAMP response to prostaglandin E2 remained unaltered .


This homologous mechanism of H2 receptor desensitization was time dependent .

This homologous mechanism of <protein>H2 receptor</protein> desensitization was time dependent .


These results indicate that histamine activates several mechanisms involved in the induction of differentiation , such as cAMP and c-fos production , but fails to promote differentiation of U937 cells , apparently due to the rapid desensitization of H2 receptors .

These results indicate that histamine activates several mechanisms involved in the induction of differentiation , such as cAMP and <dna>c-fos</dna> production , but fails to promote differentiation of <cell_line>U937 cells</cell_line> , apparently due to the rapid desensitization of <protein>H2 receptors</protein> .


Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets .

Induction of <protein>cytokine</protein> expression in <cell_type>leukocytes</cell_type> by binding of <cell_type>thrombin-stimulated platelets</cell_type> .


BACKGROUND : Activated platelets tether and activate myeloid leukocytes .

BACKGROUND : <cell_type>Activated platelets</cell_type> tether and activate <cell_type>myeloid leukocytes</cell_type> .


To investigate the potential relevance of this mechanism in acute myocardial infarction ( AMI ) , we examined cytokine induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI .

To investigate the potential relevance of this mechanism in acute myocardial infarction ( AMI ) , we examined <protein>cytokine</protein> induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI .


METHODS AND RESULTS : We obtained peripheral venous blood samples in 20 patients with AMI before and daily for 5 days after direct percutaneous transluminal coronary angioplasty ( PTCA ) and in 20 patients undergoing elective PTCA .


Throughout the study period , CD41 immunofluorescence of leukocytes ( flow cytometry ) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients ( mean +/- SE of fluorescence [ channels ] before PTCA : 77 +/- 16 versus 35 +/- 9 ; P = .003 ) .

Throughout the study period , CD41 immunofluorescence of <cell_type>leukocytes</cell_type> ( flow cytometry ) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients ( mean +/- SE of fluorescence [ channels ] before PTCA : 77 +/- 16 versus 35 +/- 9 ; P = .003 ) .


In vitro , thrombin-stimulated fixed platelets bound to neutrophils and monocytes .

In vitro , <cell_type>thrombin-stimulated fixed platelets</cell_type> bound to <cell_type>neutrophils</cell_type> and <cell_type>monocytes</cell_type> .


Within 2 hours , this resulted in increased mRNA for interleukin ( IL ) , 1 beta , IL-8 , and monocyte chemoattractant protein ( MCP ) -1 in unfractionated leukocytes .

Within 2 hours , this resulted in increased mRNA for <protein>interleukin ( IL ) , 1 beta</protein> , <protein>IL-8</protein> , and <protein>monocyte chemoattractant protein ( MCP ) -1</protein> in unfractionated <cell_type>leukocytes</cell_type> .


After 4 hours , IL-1 beta and IL-8 concentration of the cell-free supernatant had increased by 268 +/- 36 % and 210 +/- 7 % , respectively , and cellular MCP-1 content had increased by 170 +/- 8 % .

After 4 hours , <protein>IL-1 beta</protein> and <protein>IL-8</protein> concentration of the cell-free supernatant had increased by 268 +/- 36 % and 210 +/- 7 % , respectively , and cellular <protein>MCP-1</protein> content had increased by 170 +/- 8 % .


Addition of activated platelets to adherent monocytes had a similar effect and was associated with nuclear factor-kappa B activation .

Addition of <cell_type>activated platelets</cell_type> to adherent <cell_type>monocytes</cell_type> had a similar effect and was associated with <protein>nuclear factor-kappa B</protein> activation .


Inhibition of binding by anti-P selectin antibodies reduced the effect of activated platelets on cytokine production .

Inhibition of binding by <protein>anti-P selectin antibodies</protein> reduced the effect of <cell_type>activated platelets</cell_type> on <protein>cytokine</protein> production .


CONCLUSIONS : In patients with AMI , leukocyte-platelet adhesion is increased .


Binding of activated platelets induces IL-1 beta , IL-8 , and MCP-1 in leukocytes .

Binding of <cell_type>activated platelets</cell_type> induces <protein>IL-1 beta</protein> , <protein>IL-8</protein> , and <protein>MCP-1</protein> in <cell_type>leukocytes</cell_type> .


Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI .


Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response .

Immediate early and <protein>early lytic cycle proteins</protein> are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response .


Epstein-Barr virus ( EBV ) , a human gamma-herpesvirus , can establish both nonproductive ( latent ) and productive ( lytic ) infections .


Although the CD8+ cytotoxic T lymphocyte ( CTL ) response to latently infected cells is well characterized , very little is known about T cell controls over lytic infection ; this imbalance in our understanding belies the importance of virus-replicative lesions in several aspects of EBV disease pathogenesis .

Although the CD8+ cytotoxic T lymphocyte ( CTL ) response to <cell_type>latently infected cells</cell_type> is well characterized , very little is known about T cell controls over lytic infection ; this imbalance in our understanding belies the importance of virus-replicative lesions in several aspects of EBV disease pathogenesis .


The present work shows that the primary CD8+ CTL response to EBV in infectious mononucleosis patients contains multiple lytic antigen-specific reactivities at levels at least as high as those seen against latent antigens ; similar reactivities are also detectable in CTL memory .

The present work shows that the primary CD8+ CTL response to EBV in infectious mononucleosis patients contains multiple lytic antigen-specific reactivities at levels at least as high as those seen against <protein>latent antigens</protein> ; similar reactivities are also detectable in CTL memory .


Clonal analysis revealed individual responses to the two immediate early proteins BZLF1 and BRLF1 , and to three ( BMLF1 , BMRF1 , and BALF2 ) of the six early proteins tested .

Clonal analysis revealed individual responses to the two <protein>immediate early proteins</protein> <protein>BZLF1</protein> and <protein>BRLF1</protein> , and to three ( <protein>BMLF1</protein> , <protein>BMRF1</protein> , and <protein>BALF2</protein> ) of the six <protein>early proteins</protein> tested .


In several cases , the peptide epitope and HLA-restricting determinant recognized by these CTLs has been defined , one unusual feature being the number of responses restricted through HLA-C alleles .

In several cases , the peptide epitope and HLA-restricting determinant recognized by these <cell_type>CTLs</cell_type> has been defined , one unusual feature being the number of responses restricted through <dna>HLA-C alleles</dna> .


The work strongly suggests that EBV-replicative lesions are subject to direct CTL control in vivo and that immediate early and early proteins are frequently the immunodominant targets .

The work strongly suggests that EBV-replicative lesions are subject to direct CTL control in vivo and that <protein>immediate early and early proteins</protein> are frequently the immunodominant targets .


This contrasts with findings in alpha- and beta- herpesvirus systems ( herpes simplex , cytomegalovirus ) where viral interference with the antigen-processing pathway during lytic infection renders immediate early and early proteins much less immunogenic .

This contrasts with findings in alpha- and beta- herpesvirus systems ( herpes simplex , cytomegalovirus ) where viral interference with the antigen-processing pathway during lytic infection renders <protein>immediate early and early proteins</protein> much less immunogenic .


The unique capacity of gamma-herpesvirus to amplify the viral load in vivo through a latent growth-transforming infection may have rendered these agents less dependent upon viral replication as a means of successfully colonizing their hosts .


Triggering of HLA-DR antigens differentially modulates tumor necrosis factor alpha release by B cells at distinct stage of maturation .

Triggering of <protein>HLA-DR antigens</protein> differentially modulates <protein>tumor necrosis factor alpha</protein> release by <cell_type>B cells</cell_type> at distinct stage of maturation .


Triggering of HLA class II antigens by the anti-HLA-DR monoclonal antibody ( mAb ) L243 significantly ( P < 0.05 ) and differentially enhanced the release of tumor necrosis factor alpha ( TNF-alpha ) by the non-Hodgkin 's lymphoma cells Ri-I , Ci-I , and Sc-I , which are at a distinct stage of B-cell differentiation , and by the more mature Burkitt lymphoma cell Raji ; in contrast , it did not induce TNF-alpha release by the pre-B leukemia cells Nalm-6 and BV173 .

Triggering of <protein>HLA class II antigens</protein> by the <protein>anti-HLA-DR monoclonal antibody ( mAb ) L243</protein> significantly ( P < 0.05 ) and differentially enhanced the release of <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) by the <cell_type>non-Hodgkin 's lymphoma cells</cell_type> <cell_line>Ri-I</cell_line> , <cell_line>Ci-I</cell_line> , and <cell_line>Sc-I</cell_line> , which are at a distinct stage of B-cell differentiation , and by the more mature <cell_line>Burkitt lymphoma cell Raji</cell_line> ; in contrast , it did not induce <protein>TNF-alpha</protein> release by the <cell_type>pre-B leukemia cells</cell_type> <cell_line>Nalm-6</cell_line> and <cell_line>BV173</cell_line> .


TNF-alpha release peaked at 24 h and decreased thereafter , and it was dose dependent and preceded by an increase of TNF-alpha mRNA detectable after 3 h of stimulation with mAb L243 .

<protein>TNF-alpha</protein> release peaked at 24 h and decreased thereafter , and it was dose dependent and preceded by an increase of <rna>TNF-alpha mRNA</rna> detectable after 3 h of stimulation with <protein>mAb L243</protein> .


Secreted TNF-alpha mediated the enhancement of nuclear factor kappa B ( NF-kappa B ) and activator protein-1 ( AP-1 ) binding activity ; in fact , the triggering of HLA-DR antigens in the presence of antihuman TNF-alpha-neutralizing antibodies did not upregulate NF-kappa B and AP-1 .

Secreted <protein>TNF-alpha</protein> mediated the enhancement of <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) and activator protein-1 ( <protein>AP-1</protein> ) binding activity ; in fact , the triggering of <protein>HLA-DR antigens</protein> in the presence of <protein>antihuman TNF-alpha-neutralizing antibodies</protein> did not upregulate <protein>NF-kappa B</protein> and <protein>AP-1</protein> .


In contrast , released TNF-alpha was not responsible for the homotypic aggregation of Ri-I , Ci-I , Sc-I , and Raji cells induced by mAb L243 , and it did not affect the proliferation of B cells investigated .

In contrast , released <protein>TNF-alpha</protein> was not responsible for the homotypic aggregation of <cell_line>Ri-I</cell_line> , <cell_line>Ci-I</cell_line> , <cell_line>Sc-I</cell_line> , and <cell_line>Raji cells</cell_line> induced by <protein>mAb L243</protein> , and it did not affect the proliferation of <cell_type>B cells</cell_type> investigated .


Altogether , our data demonstrate that : ( a ) the ability of B cells to release TNF-alpha after triggering of HLA-DR antigens depends on their stage of differentiation ; ( b ) levels of released TNF-alpha seem to correlate with the stage of B-cell maturation but do not correlate with the amounts of cell surface HLA-DR antigens ; ( c ) secreted TNF-alpha regulates the levels of expression of NF-kappa B and AP-1 by an autocrine loop ; and ( d ) intracellular signals mediating TNF-alpha release by B cells are distinct from those regulating homotypic aggregation and proliferation .

Altogether , our data demonstrate that : ( a ) the ability of <cell_type>B cells</cell_type> to release <protein>TNF-alpha</protein> after triggering of <protein>HLA-DR antigens</protein> depends on their stage of differentiation ; ( b ) levels of released <protein>TNF-alpha</protein> seem to correlate with the stage of B-cell maturation but do not correlate with the amounts of <protein>cell surface HLA-DR antigens</protein> ; ( c ) secreted <protein>TNF-alpha</protein> regulates the levels of expression of <protein>NF-kappa B</protein> and <protein>AP-1</protein> by an autocrine loop ; and ( d ) intracellular signals mediating <protein>TNF-alpha</protein> release by <cell_type>B cells</cell_type> are distinct from those regulating homotypic aggregation and proliferation .


Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene .

<protein>Transcription factor GATA-3</protein> is differentially expressed in <cell_line>murine Th1 and Th2 cells</cell_line> and controls Th2-specific expression of the <dna>interleukin-5 gene</dna> .


Interleukin-5 ( IL-5 ) , which is produced by CD4 ( + ) T helper 2 ( Th2 ) cells , but not by Th1 cells , plays a key role in the development of eosinophilia in asthma .

<protein>Interleukin-5</protein> ( <protein>IL-5</protein> ) , which is produced by <cell_type>CD4 ( + ) T helper 2 ( Th2 ) cells</cell_type> , but not by <cell_type>Th1 cells</cell_type> , plays a key role in the development of eosinophilia in asthma .


Despite increasing evidence that the outcome of many diseases is determined by the ratio of the two subsets of CD4 ( + ) T helper cells , Th1 and Th2 , the molecular basis for Th1- and Th2- specific gene expression remains to be elucidated .

Despite increasing evidence that the outcome of many diseases is determined by the ratio of the two subsets of <cell_type>CD4 ( + ) T helper cells</cell_type> , <cell_type>Th1</cell_type> and <cell_type>Th2</cell_type> , the molecular basis for Th1- and Th2- specific gene expression remains to be elucidated .


We previously established a critical role for the transcription factor GATA-3 in IL-5 promoter activation in EL-4 cells , which express both Th1- and Th2-type cytokines .

We previously established a critical role for the <protein>transcription factor</protein> <protein>GATA-3</protein> in <dna>IL-5 promoter</dna> activation in <cell_line>EL-4 cells</cell_line> , which express both <protein>Th1- and Th2-type cytokines</protein> .


Our studies reported here demonstrate that GATA-3 is critical for expression of the IL-5 gene in bona fide Th2 cells .

Our studies reported here demonstrate that <protein>GATA-3</protein> is critical for expression of the <protein>IL-5</protein> gene in <cell_type>bona fide Th2 cells</cell_type> .


Whereas mutations in the GATA-3 site abolished antigen- or cAMP- stimulated IL-5 promoter activation in Th2 cells , ectopic expression of GATA-3 in Th1 cells or in a non-lymphoid , non-IL-5-producing cell line activated the IL-5 promoter .

Whereas mutations in the <protein>GATA-3</protein> site abolished antigen- or cAMP- stimulated IL-5 promoter activation in Th2 cells , ectopic expression of <protein>GATA-3</protein> in <cell_type>Th1 cells</cell_type> or in a <cell_line>non-lymphoid , non-IL-5-producing cell line</cell_line> activated the <dna>IL-5 promoter</dna> .


During the differentiation of naive CD4 ( + ) T cells isolated from T cell receptor transgenic mice , GATA-3 gene expression was up-regulated in developing Th2 cells , but was down-regulated in Th1 cells , and antigen- or cAMP-activated Th2 cells ( but not Th1 cells ) expressed the GATA-3 protein .

During the differentiation of <cell_type>naive CD4 ( + ) T cells</cell_type> isolated from T cell receptor transgenic mice , <protein>GATA-3</protein> gene expression was up-regulated in developing <cell_type>Th2 cells</cell_type> , but was down-regulated in <cell_type>Th1 cells</cell_type> , and <cell_type>antigen- or cAMP-activated Th2 cells</cell_type> ( but not <cell_type>Th1 cells</cell_type> ) expressed the <protein>GATA-3 protein</protein> .


Thus , GATA-3 may play an important role in the balance between Th1 and Th2 subsets in immune responses .

Thus , <protein>GATA-3</protein> may play an important role in the balance between <cell_type>Th1</cell_type> and <cell_type>Th2 subsets</cell_type> in immune responses .


Inhibition of GATA-3 activity has therapeutic potential in the treatment of asthma and other hypereosinophilic diseases .

Inhibition of <protein>GATA-3</protein> activity has therapeutic potential in the treatment of asthma and other hypereosinophilic diseases .


A shortened life span of EKLF-/- adult erythrocytes , due to a deficiency of beta-globin chains , is ameliorated by human gamma-globin chains .

A shortened life span of <cell_type>EKLF-/- adult erythrocytes</cell_type> , due to a deficiency of <protein>beta-globin chains</protein> , is ameliorated by <protein>human gamma-globin chains</protein> .


Using homologous recombination , both EKLF alleles in murine embryonic stem ( ES ) cells were inactivated .

Using homologous recombination , both <dna>EKLF alleles</dna> in <cell_line>murine embryonic stem ( ES ) cells</cell_line> were inactivated .


These EKLF-/- ES cells were capable of undergoing in vitro differentiation to form definitive erythroid colonies that were similar in size and number to those formed by wild-type ES cells .

These <cell_line>EKLF-/- ES cells</cell_line> were capable of undergoing in vitro differentiation to form definitive erythroid colonies that were similar in size and number to those formed by <cell_type>wild-type ES cells</cell_type> .


However , the EKLF-/- colonies were poorly hemoglobinized and enucleated erythrocytes in these colonies contained numerous Heinz bodies .

However , the <cell_line>EKLF-/- colonies</cell_line> were poorly hemoglobinized and <cell_type>enucleated erythrocytes</cell_type> in these colonies contained numerous Heinz bodies .


Reverse transcriptase-polymerase chain reaction ( RT-PCR ) analyses revealed that adult and embryonic globin genes were appropriately regulated , with the exception of beta h1-globin , which continued to be expressed at a very low level .

Reverse transcriptase-polymerase chain reaction ( RT-PCR ) analyses revealed that adult and <dna>embryonic globin genes</dna> were appropriately regulated , with the exception of <protein>beta h1-globin</protein> , which continued to be expressed at a very low level .


The ratio of adult beta-globin/alpha-globin mRNA in the mutant ES cells was 1/15 of that in wild-type ES cells .

The ratio of <rna>adult beta-globin/alpha-globin mRNA</rna> in the <cell_line>mutant ES cells</cell_line> was 1/15 of that in <cell_type>wild-type ES cells</cell_type> .


When the EKLF-/- cells were injected into blastocysts , they did not contribute at a detectable level to the mature erythrocyte compartment of the chimeric animals , based on analysis of glucose phosphate isomerase-1 ( GPI-1 ) isozymes and hemoglobins that distinguish ES cell-derived erythrocytes from host blastocyst-derived erythrocytes .

When the <cell_line>EKLF-/- cells</cell_line> were injected into blastocysts , they did not contribute at a detectable level to the mature erythrocyte compartment of the chimeric animals , based on analysis of <protein>glucose phosphate isomerase-1 ( GPI-1 ) isozymes</protein> and hemoglobins that distinguish <cell_type>ES cell-derived erythrocytes</cell_type> from host <cell_type>blastocyst-derived erythrocytes</cell_type> .


In contrast , semiquantitative RT-PCR analysis of RNA from reticulocytes of the same chimeric animals suggested that the ES cell-derived reticulocytes were present at a level of 6 % to 8 % .

In contrast , semiquantitative RT-PCR analysis of RNA from <cell_type>reticulocytes</cell_type> of the same chimeric animals suggested that the <cell_type>ES cell-derived reticulocytes</cell_type> were present at a level of 6 % to 8 % .


This indicated that the EKLF-/- erythrocytes in adult animals must be short-lived , apparently due to the imbalance of beta- versus alpha-globin chains , leading to the precipitation of excess alpha-globin chains to form Heinz bodies .

This indicated that the <cell_line>EKLF-/- erythrocytes</cell_line> in adult animals must be short-lived , apparently due to the imbalance of <protein>beta- versus alpha-globin chains</protein> , leading to the precipitation of excess <protein>alpha-globin chains</protein> to form Heinz bodies .


Consistent with this hypothesis , the short life span was ameliorated by introduction into the EKLF-/- ES cells of a human LCR/gamma-globin gene , as evidenced by the presence of ES cell-derived reticulocytes as well as mature erythrocytes in the blood of the chimeric animals .

Consistent with this hypothesis , the short life span was ameliorated by introduction into the <cell_line>EKLF-/- ES cells</cell_line> of a <dna>human LCR/gamma-globin gene</dna> , as evidenced by the presence of <cell_type>ES cell-derived reticulocytes</cell_type> as well as <cell_type>mature erythrocytes</cell_type> in the blood of the chimeric animals .


RP1 , a new member of the adenomatous polyposis coli-binding EB1-like gene family , is differentially expressed in activated T cells .

<dna>RP1</dna> , a new member of the <dna>adenomatous polyposis coli-binding EB1-like gene family</dna> , is differentially expressed in <cell_type>activated T cells</cell_type> .


Cross-linking of the CD3 and CD28 molecules on T lymphocytes represents one of the most effective signals for T lymphocyte activation and triggering of their cytotoxic effector function .

Cross-linking of the <protein>CD3 and CD28 molecules</protein> on <cell_type>T lymphocytes</cell_type> represents one of the most effective signals for <cell_type>T lymphocyte</cell_type> activation and triggering of their cytotoxic effector function .


To identify genes that are expressed in T cells after stimulation , mRNA from T lymphocytes that had been activated by the simultaneous stimulation of the CD3 and CD28 trigger molecules was transcribed for a differential mRNA display analysis into cDNA and was compared with cDNA from CD28 -or CD3 -activated or resting lymphocytes .

To identify genes that are expressed in <cell_type>T cells</cell_type> after stimulation , mRNA from <cell_type>T lymphocytes</cell_type> that had been activated by the simultaneous stimulation of the <protein>CD3</protein> and <protein>CD28</protein> trigger molecules was transcribed for a differential mRNA display analysis into cDNA and was compared with cDNA from <protein>CD28</protein> -or <protein>CD3</protein> -activated or resting <cell_type>lymphocytes</cell_type> .


Differential expression was confirmed subsequently by Northern blot analysis .


One of the cDNA fragments expressed specifically in CD3 -and CD28 -activated T cells was designated RP1 .

One of the <dna>cDNA fragments</dna> expressed specifically in <protein>CD3</protein> -and <protein>CD28</protein> <cell_type>-activated T cells</cell_type> was designated <dna>RP1</dna> .


The predictive protein-coding region of RP1 had a significant homology to members of the recently found adenomatous polyposis coli ( APC ) protein-binding EB1 gene family , which codes for yet unknown protein ( s ) .

The <dna>predictive protein-coding region</dna> of <dna>RP1</dna> had a significant homology to members of the recently found <dna>adenomatous polyposis coli ( APC ) protein-binding EB1 gene family</dna> , which codes for yet unknown protein ( s ) .


Bacterially expressed RP1 protein revealed specific binding to wild-type but not to mutated APC protein .

Bacterially expressed <protein>RP1 protein</protein> revealed specific binding to <protein>wild-type</protein> but not to <protein>mutated APC protein</protein> .


The rapid up-regulation of RP1 mRNA in properly activated T cells suggests that this gene might belong to the immediate/early gene family , which controls the signal transduction cascade downstream of the TCR .

The rapid up-regulation of <rna>RP1 mRNA</rna> in properly <cell_type>activated T cells</cell_type> suggests that this gene might belong to the <dna>immediate/early gene family</dna> , which controls the signal transduction cascade downstream of the <protein>TCR</protein> .


As the expression level of the RP1 gene in activated T cells and a spectrum of tumor-derived cell lines correlates with the proliferative status of the cells , members of the EB1-like gene family may not only be involved in the tumorigenesis of colorectal cancers but may also play a role in the proliferative control of normal cells .

As the expression level of the <dna>RP1 gene</dna> in <cell_type>activated T cells</cell_type> and a spectrum of <cell_line>tumor-derived cell lines</cell_line> correlates with the proliferative status of the cells , members of the <dna>EB1-like gene family</dna> may not only be involved in the tumorigenesis of colorectal cancers but may also play a role in the proliferative control of <cell_type>normal cells</cell_type> .


Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors , but not with the processing of p105/ NF-kappa B1 in T cells .

Cyclosporin A interferes with the inducible degradation of <protein>NF-kappa B</protein> inhibitors , but not with the processing of p105/ <protein>NF-kappa B1</protein> in <cell_type>T cells</cell_type> .


The transcription factor NF-kappa B controls the induction of numerous cytokine promoters during the activation of T lymphocytes .

The <protein>transcription factor</protein> <protein>NF-kappa B</protein> controls the induction of numerous <dna>cytokine promoters</dna> during the activation of <cell_type>T lymphocytes</cell_type> .


Inhibition of T cell activation by the immunosuppressants cyclosporin A ( CsA ) and FK506 exerts a suppressive effect on the induction of these NF-kappa B-controlled cytokine promoters .

Inhibition of T cell activation by the immunosuppressants cyclosporin A ( CsA ) and FK506 exerts a suppressive effect on the induction of these <dna>NF-kappa B-controlled cytokine promoters</dna> .


We show for human Jurkat T leukemia cells , as well as human and mouse primary T lymphocytes , that this inhibitory effect is accompanied by an impaired nuclear translocation of the Rel proteins c-Rel , RelA/p65 and NF-kappa B1/p50 , whereas the nuclear appearance of RelB remains unaffected .

We show for <cell_line>human Jurkat T leukemia cells</cell_line> , as well as <cell_type>human and mouse primary T lymphocytes</cell_type> , that this inhibitory effect is accompanied by an impaired nuclear translocation of the <protein>Rel proteins</protein> <protein>c-Rel</protein> , <protein>RelA/p65</protein> and <protein>NF-kappa B1/p50</protein> , whereas the nuclear appearance of <protein>RelB</protein> remains unaffected .


CsA does not interfere with the synthesis of Rel proteins , but prevents the inducible degradation of cytosolic NF-kappa B inhibitors I kappa B alpha and I kappa B beta upon T cell activation .

CsA does not interfere with the synthesis of <protein>Rel proteins</protein> , but prevents the inducible degradation of <protein>cytosolic NF-kappa B inhibitors</protein> <protein>I kappa B alpha</protein> and <protein>I kappa B beta</protein> upon T cell activation .


CsA neither inhibits the processing of the NF-kappa B1 precursor p105 to p50 , nor does it `` stabilize '' the C-terminal portion of p105 , I kappa B gamma , which is degraded during p105 processing to mature p50 .

CsA neither inhibits the processing of the <protein>NF-kappa B1 precursor</protein> <protein>p105</protein> to <protein>p50</protein> , nor does it `` stabilize '' the C-terminal portion of <protein>p105</protein> , <protein>I kappa B gamma</protein> , which is degraded during <protein>p105</protein> processing to <protein>mature p50</protein> .


These results indicate that CsA interferes with a specific event in the signal-induced degradation of I kappa B alpha and I kappa B beta , but does not affect the processing of NF-kappa B1/p105 to p50 .

These results indicate that CsA interferes with a specific event in the signal-induced degradation of <protein>I kappa B alpha</protein> and <protein>I kappa B beta</protein> , but does not affect the processing of <protein>NF-kappa B1/p105</protein> to <protein>p50</protein> .


Activation of nuclear factor-kappa B by beta-amyloid peptides and interferon-gamma in murine microglia .

Activation of <protein>nuclear factor-kappa B</protein> by beta-amyloid peptides and <protein>interferon-gamma</protein> in murine microglia .


An increasing body of evidence suggests that amyloid-beta ( A beta ) peptides and microglia are crucially involved in the pathogenesis of Alzheimer 's disease .

An increasing body of evidence suggests that amyloid-beta ( A beta ) peptides and <cell_type>microglia</cell_type> are crucially involved in the pathogenesis of Alzheimer 's disease .


In an effort to further elucidate the biological effects of A beta towards microglia , we investigated the ability of A beta peptides to activate nuclear factor ( NF ) -kappa B in the N9 murine microglial cell line .

In an effort to further elucidate the biological effects of A beta towards <cell_type>microglia</cell_type> , we investigated the ability of A beta peptides to activate <protein>nuclear factor ( NF ) -kappa B</protein> in the <cell_line>N9 murine microglial cell line</cell_line> .


Co-stimulation of microglia with suboptimal concentrations of A beta ( 25-35 ) and 100 U/ml IFN gamma resulted in the detection of a specific NF-kappa B DNA-binding activity in nuclear extracts , as determined in gel mobility shift assays .

Co-stimulation of <cell_type>microglia</cell_type> with suboptimal concentrations of A beta ( 25-35 ) and 100 U/ml <protein>IFN gamma</protein> resulted in the detection of a specific <protein>NF-kappa B</protein> DNA-binding activity in nuclear extracts , as determined in gel mobility shift assays .


This response required at least 120 min to be evident and supershift experiments revealed that the NF-kappa B complex contains both RelA and p50 .

This response required at least 120 min to be evident and supershift experiments revealed that the <protein>NF-kappa B complex</protein> contains both <protein>RelA</protein> and <protein>p50</protein> .


Accordingly , immunoblot experiments showed that amongst NF-kappa B /Rel proteins , RelA and p50 are mobilized to the nucleus following microglial cell stimulation with A beta ( 25-35 ) plus IFN gamma .

Accordingly , immunoblot experiments showed that amongst <protein>NF-kappa B</protein> <protein>/Rel proteins</protein> , <protein>RelA</protein> and <protein>p50</protein> are mobilized to the nucleus following microglial cell stimulation with A beta ( 25-35 ) plus <protein>IFN gamma</protein> .


Higher concentrations of A beta ( 25-35 ) were effective by themselves in inducing NF-kappa B activation , both in the N9 microglial cell line and in rat primary microglia , as well as in human monocytes .

Higher concentrations of A beta ( 25-35 ) were effective by themselves in inducing <protein>NF-kappa B</protein> activation , both in the <cell_line>N9 microglial cell line</cell_line> and in <cell_line>rat primary microglia</cell_line> , as well as in <cell_type>human monocytes</cell_type> .


For purposes of comparison , microglia were also stimulated with bacterial LPS , a known NF-kappa B inducer .

For purposes of comparison , <cell_type>microglia</cell_type> were also stimulated with bacterial LPS , a known <protein>NF-kappa B</protein> inducer .


As expected , LPS strongly induced the formation of two NF-kappa B DNA-binding activities , one of which was identified as RelA/p50 .

As expected , LPS strongly induced the formation of two <protein>NF-kappa B</protein> DNA-binding activities , one of which was identified as <protein>RelA/p50</protein> .


The LPS response was also more rapid , as it was already evident by 40 min and remained sustained for up to 3 h .


Collectively , these findings indicate that NF-kappa B activation might constitute one of the mechanisms underlying the inducible expression of kappa B-dependent genes in microglia stimulated by A beta peptides and IFN gamma , or by LPS .

Collectively , these findings indicate that <protein>NF-kappa B</protein> activation might constitute one of the mechanisms underlying the inducible expression of <dna>kappa B-dependent genes</dna> in <cell_type>microglia</cell_type> stimulated by A beta peptides and <protein>IFN gamma</protein> , or by LPS .


Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras .

Glucocorticoid-mediated repression of <dna>cytokine gene</dna> transcription in human <protein>arteritis-SCID chimeras</protein> .


Giant cell arteritis ( GCA ) is a vasculitic syndrome that preferentially affects medium and large-sized arteries .


Glucocorticoid therapy resolves clinical symptoms within hours to days , but therapy has to be continued over several years to prevent disease relapses .


It is not known whether and how glucocorticoids affect the function of the inflammatory infiltrate or why the disease persists subclinically despite chronic treatment .


GCA is self-sustained in temporal arteries engrafted into SCID mice , providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo .


Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of IL-2 , IL-1beta , and IL-6 mRNA , and by the diminished expression of inducible NO synthase .

Administration of dexamethasone to <cell_line>temporal artery-SCID chimeras</cell_line> for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of <rna>IL-2 , IL-1beta , and IL-6 mRNA</rna> , and by the diminished expression of inducible <protein>NO synthase</protein> .


In contrast , synthesis of IFN-gamma mRNA was only slightly decreased , and expression of TGF-beta1 was unaffected .

In contrast , synthesis of <rna>IFN-gamma mRNA</rna> was only slightly decreased , and expression of <protein>TGF-beta1</protein> was unaffected .


These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB in the xenotransplanted tissue .

These findings correlated with activation of the <dna>IkappaBalpha gene</dna> and blockade of the nuclear translocation of <protein>NFkappaB</protein> in the xenotransplanted tissue .


Dose-response experiments suggested that steroid doses currently used in clinical medicine are suboptimal in repressing NFkappaB -mediated cytokine production in the inflammatory lesions .

Dose-response experiments suggested that steroid doses currently used in clinical medicine are suboptimal in repressing <protein>NFkappaB</protein> -mediated <protein>cytokine</protein> production in the inflammatory lesions .


Chronic steroid therapy was able to deplete the T cell products IL-2 and IFN-gamma , whereas the activation of tissue-infiltrating macrophages was only partially affected .

Chronic steroid therapy was able to deplete the <protein>T cell products</protein> <protein>IL-2</protein> and <protein>IFN-gamma</protein> , whereas the activation of <cell_type>tissue-infiltrating macrophages</cell_type> was only partially affected .


IL-1beta transcription was abrogated ; in contrast , TGF-beta1 mRNA synthesis was steroid resistant .

<protein>IL-1beta</protein> transcription was abrogated ; in contrast , <rna>TGF-beta1 mRNA</rna> synthesis was steroid resistant .


The persistence of TGF-beta1-transcribing macrophages , despite paralysis of T cell function , may provide an explanation for the chronicity of the disease , and may identify a novel therapeutic target in this inflammatory vasculopathy .

The persistence of <cell_type>TGF-beta1-transcribing macrophages</cell_type> , despite paralysis of T cell function , may provide an explanation for the chronicity of the disease , and may identify a novel therapeutic target in this inflammatory vasculopathy .


Defective survival and activation of thymocytes in transgenic mice expressing a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV .

Defective survival and activation of <cell_type>thymocytes</cell_type> in transgenic mice expressing a <protein>catalytically inactive form</protein> of <protein>Ca2+/calmodulin-dependent protein kinase IV</protein> .


We have generated transgenic mice that express a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV ( CaMKIV ) specifically in thymic T cells .

We have generated transgenic mice that express a <protein>catalytically inactive form</protein> of <protein>Ca2+/calmodulin-dependent protein kinase IV</protein> ( <protein>CaMKIV</protein> ) specifically in <cell_type>thymic T cells</cell_type> .


The presence of this protein results in a markedly reduced thymic cellularity , although the distribution of the remaining cells is normal based on evaluation of the CD4 and CD8 cell surface antigens that are used to gauge T cell development .

The presence of this protein results in a markedly reduced thymic cellularity , although the distribution of the remaining cells is normal based on evaluation of the <protein>CD4</protein> and <protein>CD8</protein> <protein>cell surface antigens</protein> that are used to gauge T cell development .


Isolated thymic T cells from the transgenic mice also show a dramatically decreased survival rate when evaluated in culture under conditions that do not favor activation .

Isolated <cell_type>thymic T cells</cell_type> from the transgenic mice also show a dramatically decreased survival rate when evaluated in culture under conditions that do not favor activation .


When challenged with an activating stimulus such as alpha-CD3 or a combination of phorbol ester plus ionophore , the cells are severely compromised in their ability to produce the cytokine interleukin-2 ( IL-2 ) .

When challenged with an activating stimulus such as <protein>alpha-CD3</protein> or a combination of phorbol ester plus ionophore , the cells are severely compromised in their ability to produce the <protein>cytokine</protein> <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) .


Reduction of IL-2 production is secondary to the inability to phosphorylate the cAMP response element binding protein , CREB , and induce expression of the immediate early genes such as Fos B that are required to transactivate the IL-2 promoter .

Reduction of <protein>IL-2</protein> production is secondary to the inability to phosphorylate the <protein>cAMP response element binding protein</protein> , <protein>CREB</protein> , and induce expression of the <dna>immediate early genes</dna> such as <dna>Fos B</dna> that are required to transactivate the <dna>IL-2 promoter</dna> .


Because transgene expression was regulated by the proximal promoter of the murine lck gene and this promoter is inactivated in T cells that exit the thymus , the mutant hCaMKIV is not present in peripheral T cells .

Because transgene expression was regulated by the <dna>proximal promoter</dna> of the <dna>murine lck gene</dna> and this promoter is inactivated in <cell_type>T cells</cell_type> that exit the thymus , the <protein>mutant hCaMKIV</protein> is not present in <cell_type>peripheral T cells</cell_type> .


Consequently , T lymphocytes present in the spleen can be activated normally in response to either stimulus mentioned above , demonstrating that the effects of the inactive CaMKIV on activation are reversible .

Consequently , <cell_type>T lymphocytes</cell_type> present in the spleen can be activated normally in response to either stimulus mentioned above , demonstrating that the effects of the <protein>inactive CaMKIV</protein> on activation are reversible .


Our results suggest that CaMKIV may represent a physiologically relevant CREB kinase in T cells and that the enzyme is also required to ensure normal expansion of T cells in the thymus .

Our results suggest that <protein>CaMKIV</protein> may represent a physiologically relevant <protein>CREB kinase</protein> in <cell_type>T cells</cell_type> and that the enzyme is also required to ensure normal expansion of <cell_type>T cells</cell_type> in the thymus .


Whereas the pathway responsible for this latter role is yet to be elucidated , it is unlikely to include CREB phosphorylation .

Whereas the pathway responsible for this latter role is yet to be elucidated , it is unlikely to include <protein>CREB</protein> phosphorylation .


A new mouse gene , SRG3 , related to the SWI3 of Saccharomyces cerevisiae , is required for apoptosis induced by glucocorticoids in a thymoma cell line .

A new <dna>mouse gene</dna> , <dna>SRG3</dna> , related to the <dna>SWI3</dna> of Saccharomyces cerevisiae , is required for apoptosis induced by glucocorticoids in a <cell_line>thymoma cell line</cell_line> .


We isolated a new mouse gene that is highly expressed in thymocytes , testis , and brain .

We isolated a new <dna>mouse gene</dna> that is highly expressed in <cell_type>thymocytes</cell_type> , testis , and brain .


This gene , SRG3 , showed a significant sequence homology to SWI3 , a yeast transcriptional activator , and its human homolog BAF155 .

This gene , <dna>SRG3</dna> , showed a significant sequence homology to <dna>SWI3</dna> , a <dna>yeast transcriptional activator</dna> , and its <dna>human homolog BAF155</dna> .


SRG3 encodes 1 , 100 amino acids and has 33-47 % identity with SWI3 protein over three regions .

<dna>SRG3</dna> encodes 1 , 100 amino acids and has 33-47 % identity with <protein>SWI3 protein</protein> over three regions .


The SRG3 protein contains an acidic NH2 terminus , a myb-like DNA binding domain , a leucine-zipper motif , and a proline- and glutamine-rich region at its COOH terminus .

The <protein>SRG3 protein</protein> contains an <protein>acidic NH2 terminus</protein> , a <protein>myb-like DNA binding domain</protein> , a <protein>leucine-zipper motif</protein> , and a <protein>proline- and glutamine-rich region</protein> at its <protein>COOH terminus</protein> .


Rabbit antiserum raised against a COOH-terminal polypeptide of the SRG3 recognized a protein with an apparent molecular mass of 155 kD .

Rabbit antiserum raised against a COOH-terminal polypeptide of the <dna>SRG3</dna> recognized a protein with an apparent molecular mass of 155 kD .


The serum also detected a 170-kD protein that seems to be a mouse homologue of human BAF170 .

The serum also detected a <protein>170-kD protein</protein> that seems to be a mouse homologue of <protein>human BAF170</protein> .


Immunoprecipitation of cell extract with the antiserum against the mouse SRG3 also brought down a 195-kD protein that could be recognized by an antiserum raised against human SWI2 protein .

Immunoprecipitation of cell extract with the antiserum against the <protein>mouse SRG3</protein> also brought down a <protein>195-kD protein</protein> that could be recognized by an antiserum raised against <protein>human SWI2 protein</protein> .


The results suggest that the SRG3 protein associates with a mouse SWI2 .

The results suggest that the <protein>SRG3 protein</protein> associates with a <protein>mouse SWI2</protein> .


The SRG3 protein is expressed about three times higher in thymocytes than in peripheral lymphocytes .

The <protein>SRG3 protein</protein> is expressed about three times higher in <cell_type>thymocytes</cell_type> than in <cell_type>peripheral lymphocytes</cell_type> .


The expression of anti-sense RNA to SRG3 mRNA in a thymoma cell line , S49.1 , reduced the expression level of the SRG3 protein , and decreased the apoptotic cell death induced by glucocorticoids .

The expression of <protein>anti-sense RNA</protein> to <rna>SRG3 mRNA</rna> in a <cell_line>thymoma cell line</cell_line> , <cell_line>S49.1</cell_line> , reduced the expression level of the <protein>SRG3 protein</protein> , and decreased the apoptotic cell death induced by glucocorticoids .