JNK -mediated transcriptional activation of AP-1 is the direct output of LMP -1-triggered signaling , as shown by an inducible LMP-1 mutant .

<protein>JNK</protein> -mediated transcriptional activation of <protein>AP-1</protein> is the direct output of <protein>LMP</protein> -1-triggered signaling , as shown by an inducible <protein>LMP-1 mutant</protein> .


Using a tetracycline-regulated LMP-1 allele , we demonstrate that JNK is also an effector of non-cytotoxic LMP-1 signaling in B cells , the physiological target cells of EBV .

Using a <dna>tetracycline-regulated LMP-1 allele</dna> , we demonstrate that <protein>JNK</protein> is also an effector of non-cytotoxic <protein>LMP-1</protein> signaling in <cell_type>B cells</cell_type> , the physiological target cells of EBV .


In summary , our data reveal a novel effector of LMP-1 , the SEK/ JNK / c-Jun / AP-1 pathway , which contributes to our understanding of the immortalizing and transforming potential of LMP-1 .

In summary , our data reveal a novel effector of <protein>LMP-1</protein> , the SEK/ <protein>JNK</protein> / <protein>c-Jun</protein> / <protein>AP-1</protein> pathway , which contributes to our understanding of the immortalizing and transforming potential of <protein>LMP-1</protein> .


Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water .


1. In this study we hypothesized that in individuals with certain genetic makeup , MTBE , benzene or their metabolites act as adducts and may induce programmed cell death .


2. Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene-contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene , for a period of 5 to 8 years .


For comparison , we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene .


3 . Peripheral blood lymphocytes ( PBL ) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry .

3 . <cell_type>Peripheral blood lymphocytes</cell_type> ( <cell_type>PBL</cell_type> ) of both groups were tested for the percentage of <cell_type>apoptotic cells</cell_type> and cell cycle progression using flow cytometry .


4. When apoptotic lymphocytes from exposed individuals were compared to apoptotic lymphocytes from the control group , statistically-significant differences between each mean group were detected ( 26.4 +/- 1.8 and 12.1 +/- 1.3 , respectively ) , indicating an increased rate of apoptosis in 80.5 % of exposed individuals ( P < 0.0001 , Mann-Whitney U-Test ) .

4. When <cell_type>apoptotic lymphocytes</cell_type> from exposed individuals were compared to <cell_type>apoptotic lymphocytes</cell_type> from the control group , statistically-significant differences between each mean group were detected ( 26.4 +/- 1.8 and 12.1 +/- 1.3 , respectively ) , indicating an increased rate of apoptosis in 80.5 % of exposed individuals ( P < 0.0001 , Mann-Whitney U-Test ) .


MTBE and benzene-induced apoptosis is attributed to a discrete block within the cell cycle progression .


Because cell cycle analysis showed that in PBL from chemically-exposed individuals , between 20-50 % of cells were accumulated at the S-G2/M boundaries .

Because cell cycle analysis showed that in <cell_type>PBL</cell_type> from chemically-exposed individuals , between 20-50 % of cells were accumulated at the S-G2/M boundaries .


5. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B ( NF-kappa B ) .

5. One of the <protein>signaling molecules</protein> which mediates programmed cell death is <protein>nuclear factor Kappa-B</protein> ( <protein>NF-kappa B</protein> ) .


NF-kappa B was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene .

<protein>NF-kappa B</protein> was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene .


Indeed , addition of inhibitors of NF-kappa B activation pyrrolidine dithiocarbamate ( PDTC ) , to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40 % .

Indeed , addition of inhibitors of <protein>NF-kappa B</protein> activation pyrrolidine dithiocarbamate ( PDTC ) , to the <cell_type>lymphocytes</cell_type> of the chemically-exposed group was capable of inhibiting programmed cell death by 40 % .


This reversal of apoptosis almost to the control level by inhibitor of NF-kappa B activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death .

This reversal of apoptosis almost to the control level by inhibitor of <protein>NF-kappa B</protein> activation may indicate involvement of this <protein>signaling molecule</protein> in MTBE and benzene induction of programmed cell death .


Purification and characterization of the human SR 31747A-binding protein .

Purification and characterization of the <protein>human SR 31747A-binding protein</protein> .


A nuclear membrane protein related to yeast sterol isomerase .

A <protein>nuclear membrane protein</protein> related to <protein>yeast sterol isomerase</protein> .


SR 31747A , defined as a sigma ligand , is a novel immunosuppressive agent that blocks proliferation of human and mouse lymphocytes .

SR 31747A , defined as a sigma ligand , is a novel immunosuppressive agent that blocks proliferation of <cell_type>human and mouse lymphocytes</cell_type> .


Using a radiolabeled chemical probe , we here purified a target of SR 31747A and called it SR 31747A-binding protein ( SR-BP ) .

Using a radiolabeled chemical probe , we here purified a target of SR 31747A and called it <protein>SR 31747A-binding protein</protein> ( <protein>SR-BP</protein> ) .


Purified SR-BP retained its binding properties and migrated on SDS-polyacrylamide gel as a Mr 28 , 000 protein .

<protein>Purified SR-BP</protein> retained its binding properties and migrated on SDS-polyacrylamide gel as a <protein>Mr 28 , 000 protein</protein> .


Cloning of the cDNA encoding human SR-BP shows an open reading frame for a 223-amino acid protein , which is homologous to the recently cloned sigma 1 receptor .

Cloning of the <dna>cDNA</dna> encoding <protein>human SR-BP</protein> shows an <dna>open reading frame</dna> for a <protein>223-amino acid protein</protein> , which is homologous to the recently cloned <protein>sigma 1 receptor</protein> .


Interestingly , the deduced amino acid sequence was found to be related to fungal C8-C7 sterol isomerase , encoded by the ERG2 gene .

Interestingly , the deduced amino acid sequence was found to be related to <protein>fungal C8-C7 sterol isomerase</protein> , encoded by the <dna>ERG2 gene</dna> .


The ERG2 gene product has been identified recently as the molecular target of SR 31747A that mediates antiproliferative effects of the drug in yeast .

The <protein>ERG2 gene product</protein> has been identified recently as the molecular target of SR 31747A that mediates antiproliferative effects of the drug in yeast .


Northern blot analysis of SR-BP gene expression revealed a single transcript of 2 kilobases which was widely expressed among organs , with the highest abundance in liver and the lowest abundance in brain .

Northern blot analysis of <protein>SR-BP</protein> gene expression revealed a single transcript of <rna>2 kilobases</rna> which was widely expressed among organs , with the highest abundance in liver and the lowest abundance in brain .


Subcellular localization analysis in various cells , using a specific monoclonal antibody raised against SR-BP , demonstrated that this protein was associated with the nuclear envelope .

Subcellular localization analysis in various cells , using a <protein>specific monoclonal antibody</protein> raised against <protein>SR-BP</protein> , demonstrated that this protein was associated with the nuclear envelope .


When studying the binding of SR 31747A on membranes from yeast expressing SR-BP , we found a pharmacological profile of sigma 1 receptors ; binding was displaced by ( + ) -pentazocine , haloperidol , and ( + ) -SKF 10 , 047 , with ( + ) -SKF 10 , 047 being a more potent competitor than ( - ) -SKF 10 , 047 .

When studying the binding of SR 31747A on membranes from yeast expressing <protein>SR-BP</protein> , we found a pharmacological profile of <protein>sigma 1 receptors</protein> ; binding was displaced by ( + ) -pentazocine , haloperidol , and ( + ) -SKF 10 , 047 , with ( + ) -SKF 10 , 047 being a more potent competitor than ( - ) -SKF 10 , 047 .


Scatchard plot analysis revealed Kd values of 7.1 nM and 0.15 nM for ( + ) -pentazocine and SR 31747A , respectively , indicating an affinity of SR-BP 50-fold higher for SR 31747A than for pentazocine .

Scatchard plot analysis revealed Kd values of 7.1 nM and 0.15 nM for ( + ) -pentazocine and SR 31747A , respectively , indicating an affinity of <protein>SR-BP</protein> 50-fold higher for SR 31747A than for pentazocine .


Additionally , we showed that pentazocine , a competitive inhibitor of SR 31747A binding , also prevents the immunosuppressive effect of SR 31747A .


Taken together , these findings strongly suggest that SR-BP represents the molecular target for SR 31747A in mammalian tissues , which could be critical for T cell proliferation .

Taken together , these findings strongly suggest that <protein>SR-BP</protein> represents the molecular target for SR 31747A in mammalian tissues , which could be critical for T cell proliferation .


Phospholipase C gamma 1 overexpression and activation induced by interferon beta in human T lymphocytes : an ISGF3 -independent response .

<protein>Phospholipase C gamma 1</protein> overexpression and activation induced by <protein>interferon beta</protein> in <cell_type>human T lymphocytes</cell_type> : an <protein>ISGF3</protein> -independent response .


Interferons exert their antiviral , antiproliferative and immunoregulatory activities by stimulating the expression of several genes .

<protein>Interferons</protein> exert their antiviral , antiproliferative and <protein>immunoregulatory</protein> activities by stimulating the expression of several genes .


Such genes disclose a common element within their promoters , defined Interferon Stimulated Response Element ( ISRE ) , which binds a nuclear factor ( s ) translocated from the cytoplasm to the nucleus ( ISGF3 ) after the binding of interferon ( IFN ) to the specific receptor .

Such genes disclose a common element within their <dna>promoters</dna> , defined <dna>Interferon Stimulated Response Element</dna> ( <dna>ISRE</dna> ) , which binds a <protein>nuclear factor</protein> ( s ) translocated from the cytoplasm to the nucleus ( <protein>ISGF3</protein> ) after the binding of <protein>interferon</protein> ( <protein>IFN</protein> ) to the specific receptor .


Here we report the induction of the synthesis and of the hydrolytic activity of phospholipase C gamma 1 ( PLC gamma 1 ) in human T lymphocytes by IFN-beta .

Here we report the induction of the synthesis and of the hydrolytic activity of <protein>phospholipase C gamma 1</protein> ( <protein>PLC gamma 1</protein> ) in <cell_type>human T lymphocytes</cell_type> by <protein>IFN-beta</protein> .


The increased level of PLC gamma 1 becomes evident after 90 min of IFN-beta treatment and is still detectable after 24 h .

The increased level of <protein>PLC gamma 1</protein> becomes evident after 90 min of <protein>IFN-beta</protein> treatment and is still detectable after 24 h .


Neither the PLC gamma 1 overexpression induced by IFN nor the increased hydrolytic activity of the enzyme appear to be affected by pretreatment of the cells with the protein tyrosine kinase inhibitor genistein , which is known to prevent the association of ISGF3 components .

Neither the <protein>PLC gamma 1</protein> overexpression induced by <protein>IFN</protein> nor the increased hydrolytic activity of the <protein>enzyme</protein> appear to be affected by pretreatment of the cells with the protein <protein>tyrosine kinase</protein> inhibitor genistein , which is known to prevent the association of <protein>ISGF3</protein> components .


These results suggest that in human T lymphocytes IFN-beta can activate other transcription factor ( s ) distinct from ISGF3 to regulate PLC gamma 1 expression .

These results suggest that in <cell_type>human T lymphocytes</cell_type> <protein>IFN-beta</protein> can activate other <protein>transcription factor</protein> ( s ) distinct from <protein>ISGF3</protein> to regulate <protein>PLC gamma 1</protein> expression .


In addition , the ability of this enzyme to hydrolyse PIP2 , also in the presence of genistein , implies the possibility that this enzyme can exert its hydrolytic activity independently of protein tyrosine kinase activation .

In addition , the ability of this <protein>enzyme</protein> to hydrolyse PIP2 , also in the presence of genistein , implies the possibility that this enzyme can exert its hydrolytic activity independently of <protein>protein tyrosine kinase</protein> activation .


Negative regulation by HLA-DO of MHC class II -restricted antigen processing .

Negative regulation by <protein>HLA-DO</protein> of <protein>MHC class II</protein> -restricted antigen processing .


HLA-DM is a major histocompatibility complex ( MHC ) class II-like molecule that facilitates antigen processing by catalyzing the exchange of invariant chain-derived peptides ( CLIP ) from class II molecules for antigenic peptides .

<protein>HLA-DM</protein> is a <protein>major histocompatibility complex ( MHC ) class II-like molecule</protein> that facilitates antigen processing by catalyzing the exchange of invariant chain-derived peptides ( CLIP ) from <protein>class II molecules</protein> for antigenic peptides .


HLA-DO is a second class II-like molecule that physically associates with HLA-DM in B cells .

<protein>HLA-DO</protein> is a second <protein>class II-like molecule</protein> that physically associates with <protein>HLA-DM</protein> in <cell_type>B cells</cell_type> .


HLA-DO was shown to block HLA-DM function .

<protein>HLA-DO</protein> was shown to block <protein>HLA-DM</protein> function .


Purified HLA-DM-DO complexes could not promote peptide exchange in vitro .

Purified <protein>HLA-DM-DO complexes</protein> could not promote peptide exchange in vitro .


Expression of HLA-DO in a class II+ and DM+ , DO- human T cell line caused the accumulation of class II-CLIP complexes , indicating that HLA-DO blocked DM function in vivo and suggesting that HLA-DO is an important modulator of class II-restricted antigen processing .

Expression of <protein>HLA-DO</protein> in a <cell_line>class II+ and DM+ , DO- human T cell line</cell_line> caused the accumulation of <protein>class II-CLIP complexes</protein> , indicating that <protein>HLA-DO</protein> blocked DM function in vivo and suggesting that <protein>HLA-DO</protein> is an important modulator of class II-restricted antigen processing .


Vitamin D receptor : no evidence for allele-specific mRNA stability in cells which are heterozygous for the Taq I restriction enzyme polymorphism .

<protein>Vitamin D receptor</protein> : no evidence for allele-specific mRNA stability in cells which are heterozygous for the <protein>Taq I restriction enzyme</protein> polymorphism .


Allelic variations of the vitamin D receptor ( VDR ) gene have been associated with the risk of developing prostate cancer in men and osteoporosis in postmenopausal women .

Allelic variations of the <dna>vitamin D receptor ( VDR ) gene</dna> have been associated with the risk of developing prostate cancer in men and osteoporosis in postmenopausal women .


Three RFLPs ( TaqI , ApaI , BsmI ) define two common haplotypes : BAt and baT .

Three <dna>RFLPs</dna> ( <dna>TaqI</dna> , <dna>ApaI</dna> , <dna>BsmI</dna> ) define two common haplotypes : BAt and baT .


of these polymorphisms change the translated protein .

of these <dna>polymorphisms</dna> change the <protein>translated protein</protein> .


Since sequence variations in the 3 ' UTR of VDR have been linked to the different haplotypes , investigators have proposed that the stability of VDR mRNA is influenced by allelic variations .

Since <dna>sequence variations</dna> in the <dna>3 ' UTR</dna> of <protein>VDR</protein> have been linked to the different haplotypes , investigators have proposed that the stability of <rna>VDR mRNA</rna> is influenced by allelic variations .


Indirect evidence suggested that allele T is less stable than allele t .

Indirect evidence suggested that <dna>allele T</dna> is less stable than <dna>allele t</dna> .


In this study , we used a RT-PCR based approach to compare the stability of the big T and small t allele in normal heterozygous lymphocytes and the heterozygous cell lines NB4 ( myeloid leukemia ) and PC-3 and DU 145 ( prostate cancers ) .

In this study , we used a RT-PCR based approach to compare the stability of the <dna>big T and small t allele</dna> in <cell_type>normal heterozygous lymphocytes</cell_type> and the <cell_line>heterozygous cell lines</cell_line> <cell_line>NB4</cell_line> ( myeloid leukemia ) and <cell_line>PC-3</cell_line> and <cell_line>DU 145</cell_line> ( prostate cancers ) .


In all three cases , we did not find a significant difference in stability .


Interestingly , we consistently observed 30 % less RT-PCR product derived from the small t allele mRNA in steady state , a finding which also speaks against a higher stability of the small t allele mRNA .

Interestingly , we consistently observed 30 % less <dna>RT-PCR product</dna> derived from the <rna>small t allele mRNA</rna> in steady state , a finding which also speaks against a higher stability of the <rna>small t allele mRNA</rna> .


These results indicate a variation in transcriptional regulation rather than mRNA stability between the alleles .

These results indicate a variation in transcriptional regulation rather than mRNA stability between the <dna>alleles</dna> .


We hypothesize that an unknown gene or genes in linkage with the polymorphisms is ( are ) responsible for the relationship between risk of prostate cancer and VDR polymorphisms .

We hypothesize that an unknown gene or genes in linkage with the <dna>polymorphisms</dna> is ( are ) responsible for the relationship between risk of prostate cancer and <protein>VDR</protein> <dna>polymorphisms</dna> .


Replication of human immunodeficiency virus-1 in primary human T cells is dependent on the autocrine secretion of tumor necrosis factor through the control of nuclear factor-kappa B activation .

Replication of human immunodeficiency virus-1 in <cell_type>primary human T cells</cell_type> is dependent on the autocrine secretion of <protein>tumor necrosis factor</protein> through the control of <protein>nuclear factor-kappa B</protein> activation .


Tumor necrosis factor ( TNF ) -alpha controls T-cell activation and is a major inducer of human immunodeficiency virus ( HIV ) -1 replication in chronically infected cells .

<protein>Tumor necrosis factor ( TNF ) -alpha</protein> controls T-cell activation and is a major inducer of human immunodeficiency virus ( HIV ) -1 replication in <cell_type>chronically infected cells</cell_type> .


Therefore , we have investigated its role in primary cultures of HIV-infected human T lymphocytes by using neutralizing anti-TNF-alpha antibodies or TNF-alpha .

Therefore , we have investigated its role in primary cultures of <cell_type>HIV-infected human T lymphocytes</cell_type> by using neutralizing <protein>anti-TNF-alpha antibodies</protein> or <protein>TNF-alpha</protein> .


Primary resting T lymphocytes produced TNF-alpha and supported HIV replication after T-cell receptor activation .

Primary resting T lymphocytes produced <protein>TNF-alpha</protein> and supported HIV replication after T-cell receptor activation .


Addition of neutralizing anti-TNF-alpha antibodies drastically reduced p24 antigen release and prevented CD4+ cell depletion associated with infection .

Addition of neutralizing <protein>anti-TNF-alpha antibodies</protein> drastically reduced <protein>p24 antigen</protein> release and prevented <protein>CD4+</protein> cell depletion associated with infection .


Anti-TNF-alpha also prevented nuclear factor-kappa B ( NF-kappa B ) activation , and a good correlation between this inhibition and inhibition of HIV replication was observed .

<protein>Anti-TNF-alpha</protein> also prevented <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) activation , and a good correlation between this inhibition and inhibition of HIV replication was observed .


Moreover , supplementing the cultures with high doses of IL-2 reverted anti- TNF-alpha inhibition of cell proliferation but did not affect the inhibition of HIV p24 antigen release or NF-kappa B activation in the same cultures .

Moreover , supplementing the cultures with high doses of IL-2 reverted anti- <protein>TNF-alpha</protein> inhibition of cell proliferation but did not affect the inhibition of HIV <protein>p24 antigen</protein> release or <protein>NF-kappa B</protein> activation in the same cultures .


Moreover , anti-TNF-alpha inhibited HIV-1 long terminal repeat ( LTR ) -driven transcription of a reporter gene in primary T cells in response to activation , either in the presence or the absence of HIV-1 Tat .

Moreover , <protein>anti-TNF-alpha</protein> inhibited <dna>HIV-1 long terminal repeat</dna> ( <dna>LTR</dna> ) -driven transcription of a <dna>reporter gene</dna> in <cell_type>primary T cells</cell_type> in response to activation , either in the presence or the absence of <protein>HIV-1 Tat</protein> .


Our results support an important role for autocrine TNF-alpha secretion in controlling HIV replication in primary T cells because of its ability to maintain NF-kappa B elevated in the nucleus of T cells .

Our results support an important role for autocrine <protein>TNF-alpha</protein> secretion in controlling HIV replication in <cell_type>primary T cells</cell_type> because of its ability to maintain <protein>NF-kappa B</protein> elevated in the nucleus of <cell_type>T cells</cell_type> .


Hypoxia enhances induction of endothelial ICAM-1 : role for metabolic acidosis and proteasomes .

Hypoxia enhances induction of <protein>endothelial ICAM-1</protein> : role for metabolic acidosis and <protein>proteasomes</protein> .


Intercellular adhesion molecule 1 ( ICAM-1 ) is an important molecule in promotion of polymorphonuclear neutrophil transendothelial migration during inflammation .

<protein>Intercellular adhesion molecule 1</protein> ( <protein>ICAM-1</protein> ) is an important molecule in promotion of polymorphonuclear neutrophil transendothelial migration during inflammation .


Coincident with many inflammatory diseases is tissue hypoxia .


Thus we hypothesized that combinations of hypoxia and inflammatory stimuli may differentially regulate expression of endothelial ICAM-1 .

Thus we hypothesized that combinations of hypoxia and inflammatory stimuli may differentially regulate expression of <protein>endothelial ICAM-1</protein> .


Human endothelial cells were exposed to hypoxia in the presence or absence of added lipopolysaccharide ( LPS ) and examined for expression of functional ICAM-1 .

<cell_type>Human endothelial cells</cell_type> were exposed to hypoxia in the presence or absence of added lipopolysaccharide ( LPS ) and examined for expression of functional <protein>ICAM-1</protein> .


Although hypoxia alone did not induce ICAM-1 , the combination of LPS and hypoxia enhanced ( 3 +/- 0.4-fold over normoxia ) ICAM-1 expression .

Although hypoxia alone did not induce <protein>ICAM-1</protein> , the combination of LPS and hypoxia enhanced ( 3 +/- 0.4-fold over normoxia ) <protein>ICAM-1</protein> expression .


Combinations of hypoxia and LPS significantly increased lymphocyte binding , and such increases were inhibited by addition of anti-ICAM-1 antibodies or antisense oligonucleotides .

Combinations of hypoxia and LPS significantly increased lymphocyte binding , and such increases were inhibited by addition of <protein>anti-ICAM-1 antibodies</protein> or antisense oligonucleotides .


Hypoxic endothelia showed a > 10-fold increase in sensitivity to inhibitors of proteasome activation , and combinations of hypoxia and LPS enhanced proteasome -dependent cytoplasmic-to-nuclear localization of the nuclear transcription factor-kappa B p65 ( Rel A ) subunit .

Hypoxic endothelia showed a > 10-fold increase in sensitivity to inhibitors of <protein>proteasome</protein> activation , and combinations of hypoxia and LPS enhanced <protein>proteasome</protein> -dependent cytoplasmic-to-nuclear localization of the <protein>nuclear transcription factor-kappa B p65 ( Rel A ) subunit</protein> .


Such proteasome activation correlated with hypoxia-evoked decreases in both extracellular and intracellular pH .

Such <protein>proteasome</protein> activation correlated with hypoxia-evoked decreases in both extracellular and intracellular pH .


We conclude from these studies that endothelial hypoxia provides a novel , proteasome -dependent stimulus for ICAM-1 induction .

We conclude from these studies that endothelial hypoxia provides a novel , <protein>proteasome</protein> -dependent stimulus for <protein>ICAM-1</protein> induction .


Differanisole A , a novel antitumor antibiotic , enhances growth inhibition and differentiation of human myeloid leukemia cells induced by 9-cis retinoic acid .

Differanisole A , a novel antitumor antibiotic , enhances growth inhibition and differentiation of <cell_type>human myeloid leukemia cells</cell_type> induced by 9-cis retinoic acid .


Differanisole A , 3 , 5-dichloro-2-hydroxy-4-methoxy-6-n-propylbenzoic acid , inhibited growth of human myeloid leukemia cells .

Differanisole A , 3 , 5-dichloro-2-hydroxy-4-methoxy-6-n-propylbenzoic acid , inhibited growth of <cell_type>human myeloid leukemia cells</cell_type> .


The compound induced G1 arrest and granulocytic differentiation of HL-60 cells , although the differentiation-inducing effect was modest .

The compound induced G1 arrest and granulocytic differentiation of <cell_line>HL-60 cells</cell_line> , although the differentiation-inducing effect was modest .


Differanisole A and 9-cis retinoic acid ( 9cisRA ) synergistically inhibited the growth and induced functional and morphologic differentiation of HL-60 and NB4 cells , whereas the combined treatment with differanisole A and all-trans retinoic acid or 1alpha , 25-dihydroxyvitamin D3 was less effective .

Differanisole A and 9-cis retinoic acid ( 9cisRA ) synergistically inhibited the growth and induced functional and morphologic differentiation of <cell_line>HL-60 and NB4 cells</cell_line> , whereas the combined treatment with differanisole A and all-trans retinoic acid or 1alpha , 25-dihydroxyvitamin D3 was less effective .


Similar results were obtained in primary culture of leukemia cells from a patient with acute promyelocytic leukemia .

Similar results were obtained in primary culture of <cell_type>leukemia cells</cell_type> from a patient with acute promyelocytic leukemia .


The synergistic effect on growth inhibition and induction of differentiation required simultaneous treatment with differanisole A and 9cisRA .


Differanisole A and an RXR-specific ligand ( Ro47-5944 ) cooperatively inhibited the cell growth , while the combined effect of differanisole A and an RAR-specific ligand Am80 was just additive .


Differanisole A in combination with 9cisRA may have implications for therapy of acute promyelocytic leukemia patients .


The activation of the JAK2 /STAT5 pathway is commonly involved in signaling through the human IL-5 receptor .

The activation of the <protein>JAK2</protein> <protein>/STAT5</protein> pathway is commonly involved in signaling through the <protein>human IL-5 receptor</protein> .


The JAK ( Janus kinase ) family of protein tyrosine kinases and the STATs ( signal transducers and activators of transcription ) have been shown to be activated in response to a number of cytokines and growth factors .

The <protein>JAK ( Janus kinase ) family</protein> of <protein>protein tyrosine kinases</protein> and the <protein>STATs</protein> ( <protein>signal transducers and activators of transcription</protein> ) have been shown to be activated in response to a number of <protein>cytokines</protein> and <protein>growth factors</protein> .


In this study , we evaluated the activation of JAK /STAT pathway upon human interleukin-5 ( hIL-5 ) stimulation of two different hIL-5-responsive cell lines , hIL-5 receptor alpha-subunit ( hIL-5R alpha ) cDNA-transfected TF-1 ( TF-h5R alpha ) and butyric-acid-treated YY-1 ( YY-Bu ) , and peripheral eosinophils .

In this study , we evaluated the activation of <protein>JAK</protein> <protein>/STAT</protein> pathway upon <protein>human interleukin-5</protein> ( <protein>hIL-5</protein> ) stimulation of two different <cell_line>hIL-5-responsive cell lines</cell_line> , <cell_line>hIL-5 receptor alpha-subunit ( hIL-5R alpha ) cDNA-transfected TF-1</cell_line> ( <cell_line>TF-h5R alpha</cell_line> ) and <cell_line>butyric-acid-treated YY-1</cell_line> ( <cell_line>YY-Bu</cell_line> ) , and <cell_line>peripheral eosinophils</cell_line> .


Immunoprecipitation and electrophoretic mobility shift analysis revealed that tyrosine phosphorylation of JAK2 and activation of STAT5 were induced upon stimulation with hIL-5 in all three cell types , while STAT1 activation was only observed in eosinophils .

Immunoprecipitation and electrophoretic mobility shift analysis revealed that tyrosine phosphorylation of <protein>JAK2</protein> and activation of <protein>STAT5</protein> were induced upon stimulation with <protein>hIL-5</protein> in all three cell types , while <protein>STAT1</protein> activation was only observed in <cell_type>eosinophils</cell_type> .


These results indicate that JAK2 /STAT5 activation is a common JAK /STAT pathway for hIL-5 -mediated signal in these cells .

These results indicate that <protein>JAK2</protein> <protein>/STAT5</protein> activation is a common <protein>JAK</protein> <protein>/STAT</protein> pathway for <protein>hIL-5</protein> -mediated signal in these cells .


Dysregulation of monocytic nuclear factor-kappa B by oxidized low-density lipoprotein .

Dysregulation of <protein>monocytic nuclear factor-kappa B</protein> by oxidized <protein>low-density lipoprotein</protein> .


Nuclear factor-kappa B ( NF-kappa B ) /Rel transcription factors may be involved in atherosclerosis , as is suggested by the presence of activated NF-kappa B in human atherosclerotic lesions .

<protein>Nuclear factor-kappa B ( NF-kappa B ) /Rel transcription factors</protein> may be involved in atherosclerosis , as is suggested by the presence of activated <protein>NF-kappa B</protein> in human atherosclerotic lesions .


The aim of the present study was to investigate the effects of oxidized LDL ( oxLDL ) on the NF-kappa B system in human THP-1 monocytic cells as well as adherent monocytes .

The aim of the present study was to investigate the effects of <protein>oxidized LDL</protein> ( <protein>oxLDL</protein> ) on the <protein>NF-kappa B</protein> system in human <cell_line>THP-1 monocytic cells</cell_line> as well as <cell_type>adherent monocytes</cell_type> .


Our results demonstrate that short-term incubation of these cells with oxLDL activated p50/p65 containing NF-kappa B dimers and induced the expression of the target gene IL-8 .

Our results demonstrate that short-term incubation of these cells with <protein>oxLDL activated p50/p65</protein> containing <protein>NF-kappa B dimers</protein> and induced the expression of the <dna>target gene IL-8</dna> .


This activation of NF-kappa B was inhibited by the antioxidant and H2O2 scavenger pyrrolidine dithiocarbamate and the proteasome inhibitor PSI .

This activation of <protein>NF-kappa B</protein> was inhibited by the antioxidant and H2O2 scavenger pyrrolidine dithiocarbamate and the <protein>proteasome</protein> inhibitor PSI .


The oxLDL -induced NF-kappa B activation was accompanied by an initial depletion of I kappa B-alpha followed by a slight transient increase in the level of this inhibitor protein .

The <protein>oxLDL</protein> -induced <protein>NF-kappa B</protein> activation was accompanied by an initial depletion of <protein>I kappa B-alpha</protein> followed by a slight transient increase in the level of this inhibitor protein .


In contrast , long-term treatment with oxLDL prevented the lipopolysaccharide-induced depletion of I kappa B-alpha , accompanied by an inhibition of both NF-kappa B activation and the expression of tumor necrosis factor-alpha and interleukin-1 beta genes .

In contrast , long-term treatment with <protein>oxLDL</protein> prevented the lipopolysaccharide-induced depletion of <protein>I kappa B-alpha</protein> , accompanied by an inhibition of both <protein>NF-kappa B</protein> activation and the expression of <dna>tumor necrosis factor-alpha and interleukin-1 beta genes</dna> .


These observations provide additional evidence that oxLDL is a potent modulator of gene expression and suggest that ( dys ) regulation of NF-kappa B/Rel is likely to play an important role in atherogenesis .

These observations provide additional evidence that <protein>oxLDL</protein> is a potent modulator of gene expression and suggest that ( dys ) regulation of <protein>NF-kappa B/Rel</protein> is likely to play an important role in atherogenesis .


Suppression of nuclear factor kappa B and CD18 -mediated leukocyte adhesion to the corneal endothelium by dexamethasone .

Suppression of <protein>nuclear factor kappa B</protein> and <protein>CD18</protein> -mediated leukocyte adhesion to the corneal endothelium by dexamethasone .


PURPOSE : To demonstrate that leukocyte adhesion to cultured corneal endothelial cells is mediated by the CD18 antigen , and to determine whether dexamethasone directly suppresses adhesion by inhibiting activation of nuclear factor kappa B ( NFkappaB ) .

PURPOSE : To demonstrate that leukocyte adhesion to <cell_line>cultured corneal endothelial cells</cell_line> is mediated by the <protein>CD18 antigen</protein> , and to determine whether dexamethasone directly suppresses adhesion by inhibiting activation of <protein>nuclear factor kappa B</protein> ( <protein>NFkappaB</protein> ) .


METHODS : Cultured bovine corneal endothelium was stimulated for 6 hours by 40 micron/ml tumor necrosis factor alpha ( TNFalpha ) .

METHODS : Cultured bovine corneal endothelium was stimulated for 6 hours by 40 micron/ml <protein>tumor necrosis factor alpha</protein> ( <protein>TNFalpha</protein> ) .


Dexamethasone was added 1 hour before TNFalpha stimulation in the dexamethasone group .

Dexamethasone was added 1 hour before <protein>TNFalpha</protein> stimulation in the dexamethasone group .


After stimulation , neutrophils separated from a healthy human volunteer were added with or without anti-CD18 antibody .

After stimulation , neutrophils separated from a healthy human volunteer were added with or without <protein>anti-CD18 antibody</protein> .


The culture plate was settled for 15 minutes at 37 degrees C , and then neutrophils were activated by N-formyl-methionyl-leucyl-phenylalanine for 5 minutes .

The culture plate was settled for 15 minutes at 37 degrees C , and then <cell_type>neutrophils</cell_type> were activated by N-formyl-methionyl-leucyl-phenylalanine for 5 minutes .


Nonadherent neutrophils were removed by sealing and inverting the culture well .

Nonadherent <cell_type>neutrophils</cell_type> were removed by sealing and inverting the culture well .


The intracellular localization of NFkappaB after TNFalpha simulation was determined by confocal immunocytochemistry using an anti-p65 antibody .

The intracellular localization of <protein>NFkappaB</protein> after <protein>TNFalpha</protein> simulation was determined by confocal immunocytochemistry using an <protein>anti-p65 antibody</protein> .


RESULTS : Neutrophil adhesion to cultured corneal endothelial cells increased significantly on exposure to TNFalpha ( 451.4+/-45.4 cells/mm2 , n = 16 ) compared to control ( 156.7+/-27.3 cells/mm2 , n = 16 , P < 0.01 ) .

RESULTS : Neutrophil adhesion to <cell_line>cultured corneal endothelial cells</cell_line> increased significantly on exposure to <protein>TNFalpha</protein> ( 451.4+/-45.4 cells/mm2 , n = 16 ) compared to control ( 156.7+/-27.3 cells/mm2 , n = 16 , P < 0.01 ) .


This increased adhesion was suppressed by the addition of anti-CD18 antibody ( 157.6+/-25.1 cells/mm2 , n = 8 , P < 0.01 ) and by pretreatment with 10 ( -7 ) M dexamethasone ( 207.9+/-31.5 cells/mm2 , n = 10 , P < 0.01 ) .

This increased adhesion was suppressed by the addition of <protein>anti-CD18 antibody</protein> ( 157.6+/-25.1 cells/mm2 , n = 8 , P < 0.01 ) and by pretreatment with 10 ( -7 ) M dexamethasone ( 207.9+/-31.5 cells/mm2 , n = 10 , P < 0.01 ) .


Immunocytochemistry 60 minutes after stimulation revealed that NFkappaB was located in the cytoplasm in unstimulated cells ; however , the addition of TNFalpha caused NFkappaB to translocate into the nucleus .

Immunocytochemistry 60 minutes after stimulation revealed that <protein>NFkappaB</protein> was located in the cytoplasm in <cell_type>unstimulated cells</cell_type> ; however , the addition of <protein>TNFalpha</protein> caused <protein>NFkappaB</protein> to translocate into the nucleus .


Pretreatment with dexamethasone tapered NFkappaB translocation into the nucleus .

Pretreatment with dexamethasone tapered <protein>NFkappaB</protein> translocation into the nucleus .


CONCLUSIONS : Leukocyte adhesion to the corneal endothelium was shown to be mediated by CD18 expressed on activated leukocytes .

CONCLUSIONS : Leukocyte adhesion to the corneal endothelium was shown to be mediated by <protein>CD18</protein> expressed on <cell_type>activated leukocytes</cell_type> .


Pretreatment of the endothelium with dexamethasone inhibited leukocyte adhesion ; this may be due in part to the suppression of NFkappaB entry into the nucleus .

Pretreatment of the endothelium with dexamethasone inhibited leukocyte adhesion ; this may be due in part to the suppression of <protein>NFkappaB</protein> entry into the nucleus .


Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans .

Molecular characterization and pattern of tissue expression of the gene for <protein>neutrophil gelatinase-associated lipocalin</protein> from humans .


Neutrophil gelatinase-associated lipocalin ( NGAL ) is a 25-kDa lipocalin first identified as a protein stored in specific granules of the human neutrophil .

<protein>Neutrophil gelatinase-associated lipocalin</protein> ( <protein>NGAL</protein> ) is a <protein>25-kDa lipocalin</protein> first identified as a protein stored in specific granules of the <cell_type>human neutrophil</cell_type> .


The protein is believed to bind small lipophilic substances such as bacterial derived formylpeptides and lipopolysaccharides ( LPS ) and might function as a modulator of inflammation .


To characterize the regulation of NGAL further , we have cloned and sequenced a 5869-bp region of the NGAL gene including 1695 bp of the 5 ' nontranscribed region and a 3696-bp coding region encompassing seven exons and six introns .

To characterize the regulation of <protein>NGAL</protein> further , we have cloned and sequenced a <dna>5869-bp region</dna> of the <dna>NGAL gene</dna> including 1695 bp of the <dna>5 ' nontranscribed region</dna> and a <dna>3696-bp coding region</dna> encompassing <dna>seven exons and six introns</dna> .


The transcriptional start sites were identified by an RNase protection assay .

The <dna>transcriptional start sites</dna> were identified by an <protein>RNase</protein> protection assay .


The NGAL gene is highly homologous to the mouse gene 24p3 .

The <protein>NGAL</protein> gene is highly homologous to the <dna>mouse gene 24p3</dna> .


NGAL was expressed in bone marrow and in tissues that are prone to exposure to microorganisms .

<protein>NGAL</protein> was expressed in bone marrow and in tissues that are prone to exposure to microorganisms .


Potential cis-acting elements were identified in the promoter region of the NGAL gene by computer analysis and include binding sites for CTF/CBP , the hematopoietic transcription factors GATA-1 and PU.1 , and the LPS-inducible factor NF-kappa B .

Potential <dna>cis-acting elements</dna> were identified in the <dna>promoter region</dna> of the <dna>NGAL gene</dna> by computer analysis and include <dna>binding sites</dna> for <protein>CTF/CBP</protein> , the <protein>hematopoietic transcription factors</protein> <protein>GATA-1</protein> and <protein>PU.1</protein> , and the <protein>LPS-inducible factor NF-kappa B</protein> .


Human neutrophils express GH-N gene transcripts and the pituitary transcription factor Pit-1b .

<cell_type>Human neutrophils</cell_type> express <rna>GH-N gene transcripts</rna> and the <protein>pituitary transcription factor</protein> <protein>Pit-1b</protein> .


Since GH stimulates the development and function of granulocytes , we investigated the expression of GH in granulocyte subsets .

Since <protein>GH</protein> stimulates the development and function of <cell_type>granulocytes</cell_type> , we investigated the expression of <protein>GH</protein> in <cell_type>granulocyte subsets</cell_type> .


By immunocytochemistry , 25 +/- 7 % of the human neutrophils were shown to express immunoreactive GH , whereas eosinophils were negative .

By immunocytochemistry , 25 +/- 7 % of the <cell_type>human neutrophils</cell_type> were shown to express <protein>immunoreactive GH</protein> , whereas <cell_type>eosinophils</cell_type> were negative .


Reversed transcription ( RT ) -PCR analysis demonstrated GH mRNA in neutrophils .

Reversed transcription ( RT ) -PCR analysis demonstrated <rna>GH mRNA</rna> in <cell_type>neutrophils</cell_type> .


Restriction analysis revealed that neutrophils express the GH-N gene but not the GH-V gene .

Restriction analysis revealed that <cell_type>neutrophils</cell_type> express the <dna>GH-N gene</dna> but not the <dna>GH-V gene</dna> .


Furthermore , we demonstrated by western blot analysis that neutrophils express an alternatively spliced variant of the pituitary transcription factor Pit-1 , designated Pit-1b .

Furthermore , we demonstrated by western blot analysis that <cell_type>neutrophils</cell_type> express an alternatively spliced variant of the <protein>pituitary transcription factor</protein> <protein>Pit-1</protein> , designated <protein>Pit-1b</protein> .


The ability of BHRF1 to inhibit apoptosis is dependent on stimulus and cell type .

The ability of <protein>BHRF1</protein> to inhibit apoptosis is dependent on stimulus and cell type .


The development of resistance to host defense mechanisms such as tumor necrosis factor ( TNF ) - and Fas-mediated apoptosis of transformed or virus-infected cells may be a critical component in the development of disease .

The development of resistance to host defense mechanisms such as tumor necrosis factor ( TNF ) - and Fas-mediated apoptosis of <cell_type>transformed</cell_type> or <cell_type>virus-infected cells</cell_type> may be a critical component in the development of disease .


To find genes that protect cells from apoptosis , we used an expression cloning strategy and identified BHRF1 , an Epstein-Barr virus ( EBV ) early-lytic-cycle protein with distant homology to Bcl-2 , as an anti-apoptosis protein .

To find genes that protect cells from apoptosis , we used an expression cloning strategy and identified <protein>BHRF1</protein> , an <protein>Epstein-Barr virus ( EBV ) early-lytic-cycle protein</protein> with distant homology to <protein>Bcl-2</protein> , as an <protein>anti-apoptosis protein</protein> .


Expression of BHRF1 in MCF-Fas cells conferred nearly complete resistance against both anti-Fas antibody and TNF-mediated apoptosis .

Expression of <protein>BHRF1</protein> in <cell_line>MCF-Fas cells</cell_line> conferred nearly complete resistance against both <protein>anti-Fas antibody</protein> and TNF-mediated apoptosis .


In addition , BHRF1 protected these cells from monocyte-mediated killing but failed to protect them from killing mediated by lymphokine-activated killer cells .

In addition , <protein>BHRF1</protein> protected these cells from monocyte-mediated killing but failed to protect them from killing mediated by <cell_type>lymphokine-activated killer cells</cell_type> .


The ability of BHRF1 to protect MCF-Fas cells from apoptosis induced by various stimuli was identical to that of Bcl-2 and Bcl-xL .

The ability of <protein>BHRF1</protein> to protect <cell_line>MCF-Fas cells</cell_line> from apoptosis induced by various stimuli was identical to that of <protein>Bcl-2</protein> and <protein>Bcl-xL</protein> .


Moreover , the mechanism of action of BHRF1 resembled that of Bcl-2 and Bcl-xL as it inhibited TNF- and anti-Fas-induced activation of two enzymes participating in the apoptosis pathway , cytosolic phospholipase A2 and caspase-3/CPP32 , but did not interfere with the activation of NF-kappaB-like transcription factors .

Moreover , the mechanism of action of <protein>BHRF1</protein> resembled that of <protein>Bcl-2</protein> and <protein>Bcl-xL</protein> as it inhibited TNF- and anti-Fas-induced activation of two enzymes participating in the apoptosis pathway , <protein>cytosolic phospholipase A2</protein> and <protein>caspase-3/CPP32</protein> , but did not interfere with the activation of <protein>NF-kappaB-like transcription factors</protein> .


A putative function of BHRF1 in EBV-infected epithelial cells may be to protect virus-infected cells from TNF- and/or anti-Fas- induced cell death in order to maximize virus production .

A putative function of <protein>BHRF1</protein> in <cell_type>EBV-infected epithelial cells</cell_type> may be to protect virus-infected cells from TNF- and/or anti-Fas- induced cell death in order to maximize virus production .


Surprisingly , expression of neither BHRF1 nor Bcl-2 in a B-cell line , BJAB , protected the cells from anti-Fas-mediated apoptosis even though they increased the survival of serum-starved cells .

Surprisingly , expression of neither <protein>BHRF1</protein> nor <protein>Bcl-2</protein> in a <cell_line>B-cell line</cell_line> , <cell_line>BJAB</cell_line> , protected the cells from anti-Fas-mediated apoptosis even though they increased the survival of <cell_type>serum-starved cells</cell_type> .


Thus , the protective role of BHRF1 against apoptosis resembles that of Bcl-2 in being cell type specific and dependent on the apoptotic stimulus .

Thus , the protective role of <protein>BHRF1</protein> against apoptosis resembles that of <protein>Bcl-2</protein> in being cell type specific and dependent on the apoptotic stimulus .


Genomic organization , sequence , and transcriptional regulation of the human eotaxin gene .

Genomic organization , sequence , and transcriptional regulation of the <dna>human eotaxin gene</dna> .


Eotaxin is an eosinophil specific beta-chemokine assumed to be involved in eosinophilic inflammatory diseases such as atopic dermatitis , allergic rhinitis , asthma and parasitic infections .

<protein>Eotaxin</protein> is an <protein>eosinophil specific beta-chemokine</protein> assumed to be involved in eosinophilic inflammatory diseases such as atopic dermatitis , allergic rhinitis , asthma and parasitic infections .


Its expression is stimulus- and cell-specific .


We here describe the genomic organisation ( 3 exons of 132 , 112 and 542 bp and 2 introns of 1211 and 378 bp ) and sequence including 3 kb of DNA from the immediate 5 ' upstream region of the human eotaxin gene .

We here describe the genomic organisation ( 3 <dna>exons</dna> of 132 , 112 and 542 bp and 2 <dna>introns</dna> of 1211 and 378 bp ) and sequence including 3 kb of DNA from the immediate <dna>5 ' upstream region</dna> of the <dna>human eotaxin gene</dna> .


Among the regulatory promoter elements potentially regulating eotaxin gene expression and/or mediating the effects of anti-inflammatory drugs we identified consensus sequences known to interact with nuclear factors like NF-IL6 , AP-1 , a NF-kappa-B like consensus sequence and gamma-interferon- as well as glucocorticoid response elements .

Among the <dna>regulatory promoter elements</dna> potentially regulating <dna>eotaxin gene</dna> expression and/or mediating the effects of anti-inflammatory drugs we identified <dna>consensus sequences</dna> known to interact with <protein>nuclear factors</protein> like <protein>NF-IL6</protein> , <protein>AP-1</protein> , a <dna>NF-kappa-B like consensus sequence</dna> and <dna>gamma-interferon- as well as glucocorticoid response elements</dna> .


Differential interaction of nuclear factors with the leukocyte-specific pp52 promoter in B and T cells .

Differential interaction of <protein>nuclear factors</protein> with the <dna>leukocyte-specific pp52 promoter</dna> in <cell_type>B and T cells</cell_type> .


The leukocyte-specific , cytoskeleton-binding pp52 ( LSP-1 , WP-34 ) protein is widely expressed in multiple leukocyte lineages , including B and T lymphocytes , granulocytes , and macrophages .

The leukocyte-specific , cytoskeleton-binding pp52 ( LSP-1 , WP-34 ) protein is widely expressed in multiple leukocyte lineages , including <cell_type>B and T lymphocytes</cell_type> , <cell_type>granulocytes</cell_type> , and <cell_type>macrophages</cell_type> .


We previously detected a tissue-specific promoter preceding the exon encoding the N terminus of the pp52 leukocyte protein .

We previously detected a <dna>tissue-specific promoter</dna> preceding the exon encoding the <protein>N terminus</protein> of the <protein>pp52 leukocyte protein</protein> .


Here we describe the functional characterization of this promoter and identification of the factors in B and T cells that regulate its activity .

Here we describe the functional characterization of this promoter and identification of the factors in <cell_type>B and T cells</cell_type> that regulate its activity .


The pp52 promoter contains an initiator specifying the unique 5 ' terminus of pp52 mRNA , tandem pairs of Ets and SP1 motifs , and a lone C/EBP motif .

The <dna>pp52 promoter</dna> contains an initiator specifying the unique <dna>5 ' terminus</dna> of <rna>pp52 mRNA</rna> , tandem pairs of <dna>Ets and SP1 motifs</dna> , and a <dna>lone C/EBP motif</dna> .


All these motifs are essential and collectively control transcriptional activity .


DNA binding studies and Ab supershift assays revealed that different combinations of factors interact with these motifs in B cells vs T cells .

DNA binding studies and Ab supershift assays revealed that different combinations of factors interact with these motifs in <cell_type>B cells</cell_type> vs <cell_type>T cells</cell_type> .


The Ets motifs are preferentially bound by PU-1 in B cell extracts from all stages of development , whereas a different Ets family member reacts with these motifs in T cell extracts .

The <dna>Ets motifs</dna> are preferentially bound by <protein>PU-1</protein> in B cell extracts from all stages of development , whereas a different <protein>Ets family member</protein> reacts with these motifs in T cell extracts .


The C/EBP motif is bound by Ig/EBP-1 in pre-B cell and T cell extracts , but is replaced by nuclear factor-IL-6beta or a nuclear factor-IL-6beta-Ig/EBP-1 heterodimer in plasmacytoma cell extracts .

The <dna>C/EBP motif</dna> is bound by <protein>Ig/EBP-1</protein> in pre-B cell and T cell extracts , but is replaced by <protein>nuclear factor-IL-6beta</protein> or a <protein>nuclear factor-IL-6beta-Ig/EBP-1 heterodimer</protein> in plasmacytoma cell extracts .


Despite its reported role as a negative regulator of transcription , Ig/EBP-1 appears to exert a stimulatory effect on this promoter .

Despite its reported role as a negative regulator of transcription , <protein>Ig/EBP-1</protein> appears to exert a stimulatory effect on this <dna>promoter</dna> .


These findings reveal the features controlling the pp52 promoter in B and T cells and provide the foundation for determining the regulation of this promoter in other leukocyte lineages .

These findings reveal the features controlling the <dna>pp52 promoter</dna> in <cell_type>B and T cells</cell_type> and provide the foundation for determining the regulation of this <dna>promoter</dna> in other <cell_type>leukocyte lineages</cell_type> .


Regulation of B-cell commitment to plasma cells or to memory B cells .

Regulation of B-cell commitment to <cell_type>plasma cells</cell_type> or to <cell_type>memory B cells</cell_type> .


During humoral immune responses , B-lymphocyte activation is followed by differentiation along either the plasma cell pathway or the memory B-cell pathway .


Recent studies suggest that CD40-CD40 ligand , OX-OX40 ligand , a group of cytokines and intracellular transcriptional factors may all contribute to B-lymphocyte differentiation control .

Recent studies suggest that <protein>CD40-CD40 ligand</protein> , <protein>OX-OX40 ligand</protein> , a group of <protein>cytokines</protein> and intracellular transcriptional factors may all contribute to B-lymphocyte differentiation control .


Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity .

<protein>Transcription factor</protein> binding sites downstream of the <dna>human immunodeficiency virus type 1 transcription start site</dna> are important for virus infectivity .


When transcriptionally active , the human immunodeficiency virus ( HIV ) promoter contains a nucleosome-free region encompassing both the promoter/enhancer region and a large region ( 255 nucleotides [ nt ] ) downstream of the transcription start site .

When transcriptionally active , the human immunodeficiency virus ( HIV ) <dna>promoter</dna> contains a nucleosome-free region encompassing both the <dna>promoter/enhancer region</dna> and a large region ( <dna>255 nucleotides</dna> [ nt ] ) downstream of the <dna>transcription start site</dna> .


We have previously identified new binding sites for transcription factors downstream of the transcription start site ( nt 465 to 720 ) : three AP-1 sites ( I , II , and III ) , an AP3-like motif ( AP3-L ) , a downstream binding factor ( DBF ) site , and juxtaposed Sp1 sites .

We have previously identified new binding sites for <protein>transcription factors</protein> downstream of the <dna>transcription start site</dna> ( <dna>nt 465 to 720</dna> ) : three <dna>AP-1 sites</dna> ( I , II , and III ) , an <dna>AP3-like motif</dna> ( <dna>AP3-L</dna> ) , a <dna>downstream binding factor ( DBF ) site</dna> , and <dna>juxtaposed Sp1 sites</dna> .


Here , we show that the DBF site is an interferon-responsive factor ( IRF ) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT .

Here , we show that the <dna>DBF site</dna> is an <dna>interferon-responsive factor ( IRF ) binding site</dna> and that the <dna>AP3-L motif</dna> binds the <protein>T-cell-specific factor</protein> <protein>NF-AT</protein> .


Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication .


Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1 ( III ) /AP3-L did not affect HIV-1 replication compared to that of the wild-type virus .

Individual mutation of the DBF or <dna>AP3-L</dna> site as well as the double <dna>mutation AP-1 ( III ) /AP3-L</dna> did not affect HIV-1 replication compared to that of the wild-type virus .


In contrast , proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication .

In contrast , proviruses carrying mutations in the <dna>Sp1 sites</dna> were totally defective in terms of replication .


Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1 ( III ) , AP3-L , and DBF sites and in the AP3-L and DBF-sites , whereas viruses mutated in the AP-1 ( I , II , III ) and AP3-L sites and in the AP-1 ( I , II , III ) , AP3-L , and DBF sites exhibited a severely defective replicative phenotype .

Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the <dna>AP-1 ( III )</dna> , <dna>AP3-L</dna> , and <dna>DBF sites</dna> and in the <dna>AP3-L</dna> and <dna>DBF-sites</dna> , whereas viruses mutated in the <dna>AP-1 ( I , II , III )</dna> and <dna>AP3-L sites</dna> and in the AP-1 ( I , II , III ) , <dna>AP3-L</dna> , and <dna>DBF sites</dna> exhibited a severely defective replicative phenotype .


No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA .

No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their <rna>HIV genomic RNA</rna> .


Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants .

Measurement of the transcriptional activity of the <dna>HIV-1 promoter</dna> after transient transfection of the <dna>HIV-1 provirus DNA</dna> or of <dna>long terminal repeat-luciferase constructs</dna> showed a positive correlation between the transcriptional and the replication defects for most mutants .


Glucocorticoid receptor regulates expression of L-selectin and CD11/CD18 on human neutrophils [ see comments ]

<protein>Glucocorticoid receptor</protein> regulates expression of <protein>L-selectin</protein> and <protein>CD11/CD18</protein> on <cell_type>human neutrophils</cell_type> [ see comments ]


BACKGROUND : Recent studies have raised the hypothesis that glucocorticoids could diminish the ability of endothelial cells to direct leukocyte traffic into inflamed tissues by inhibiting expression of the adhesion molecules endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 .

BACKGROUND : Recent studies have raised the hypothesis that glucocorticoids could diminish the ability of <cell_type>endothelial cells</cell_type> to direct leukocyte traffic into inflamed tissues by inhibiting expression of the <protein>adhesion molecules</protein> <protein>endothelial-leukocyte adhesion molecule-1</protein> and <protein>intercellular adhesion molecule-1</protein> .


The aim of the present study was to investigate whether glucocorticoids also regulate the expression of L-selectin and CD11/CD18 integrins on human neutrophil granulocytes .

The aim of the present study was to investigate whether glucocorticoids also regulate the expression of <protein>L-selectin</protein> and <protein>CD11/CD18</protein> <protein>integrins</protein> on <cell_type>human neutrophil granulocytes</cell_type> .


METHODS AND RESULTS : Incubation of human whole blood with platelet-activating factor ( PAF , 1 mumol/L ) evoked downregulation of L-selectin and upregulation of CD11/CD18 adhesion receptors on neutrophils as measured by flow cytometry .

METHODS AND RESULTS : Incubation of human whole blood with <protein>platelet-activating factor</protein> ( <protein>PAF</protein> , 1 mumol/L ) evoked downregulation of <protein>L-selectin</protein> and upregulation of <protein>CD11/CD18</protein> <protein>adhesion receptors</protein> on neutrophils as measured by flow cytometry .


While dexamethasone ( 0.1 nmol/L to 100 mumol/L ) did not affect expression of adhesion molecules on resting neutrophils , it attenuated the PAF -induced changes in L-selectin and CD18 expression in a time- and concentration-dependent fashion with IC50 values of 31 and 13 nmol/L , respectively .

While dexamethasone ( 0.1 nmol/L to 100 mumol/L ) did not affect expression of <protein>adhesion molecules</protein> on <cell_type>resting neutrophils</cell_type> , it attenuated the <protein>PAF</protein> -induced changes in <protein>L-selectin</protein> and <protein>CD18</protein> expression in a time- and concentration-dependent fashion with IC50 values of 31 and 13 nmol/L , respectively .


These effects of dexamethasone were completely aborted by RU-486 ( 10 mumol/L ) , which blocks transcriptional activation of the glucocorticoid receptor , and by the protein synthesis inhibitor cycloheximide ( 35.5 mumol/L ) .

These effects of dexamethasone were completely aborted by RU-486 ( 10 mumol/L ) , which blocks transcriptional activation of the <protein>glucocorticoid receptor</protein> , and by the protein synthesis inhibitor cycloheximide ( 35.5 mumol/L ) .


Dexamethasone , up to a concentration of 1 mumol/L , neither affected significantly the release of granule enzymes nor interfered with PAF binding to its membrane receptors .

Dexamethasone , up to a concentration of 1 mumol/L , neither affected significantly the release of <protein>granule enzymes</protein> nor interfered with <protein>PAF</protein> binding to its <protein>membrane receptors</protein> .


CONCLUSIONS : Our results show that glucocorticoids at clinically relevant concentrations exert specific actions on expression of adhesion molecules on activated neutrophils , which are mediated through ligation of glucocorticoid receptors and induction of protein synthesis , and suggest a novel mechanism by which anti-inflammatory corticosteroids may inhibit leukocyte accumulation .

CONCLUSIONS : Our results show that glucocorticoids at clinically relevant concentrations exert specific actions on expression of <protein>adhesion molecules</protein> on <cell_type>activated neutrophils</cell_type> , which are mediated through ligation of <protein>glucocorticoid receptors</protein> and induction of protein synthesis , and suggest a novel mechanism by which anti-inflammatory corticosteroids may inhibit leukocyte accumulation .


The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites .

The immediate-early gene product <protein>Egr-1</protein> regulates the <dna>human interleukin-2 receptor beta-chain promoter</dna> through <dna>noncanonical Egr and Sp1 binding sites</dna> .


The interleukin-2 IL-2 receptor beta-chain ( IL-2Rbeta ) is an essential component of the receptors for IL-2 and IL-15 .

The <protein>interleukin-2 IL-2 receptor beta-chain</protein> ( <protein>IL-2Rbeta</protein> ) is an essential component of the receptors for <protein>IL-2</protein> and <protein>IL-15</protein> .


Although IL-2Rbeta is constitutively expressed by lymphocytes , its expression can be further induced by a number of stimuli , including phorbol 12-myristate 13-acetate ( PMA ) .

Although <protein>IL-2Rbeta</protein> is constitutively expressed by lymphocytes , its expression can be further induced by a number of stimuli , including phorbol 12-myristate 13-acetate ( PMA ) .


We have now characterized factors that bind to an enhancer region located between nucleotides -170 and -139 of the human IL-2Rbeta promoter .

We have now characterized factors that bind to an enhancer region located between <dna>nucleotides -170 and -139</dna> of the human <dna>IL-2Rbeta promoter</dna> .


Both Sp1 and Sp3 bound to the 5 ' portion of this region , whereas a PMA-inducible factor ( PIF ) mainly bound to its 3 ' portion and bound to the Sp binding motifs as well .

Both <protein>Sp1</protein> and <protein>Sp3</protein> bound to the <dna>5 ' portion</dna> of this region , whereas a <protein>PMA-inducible factor</protein> ( <protein>PIF</protein> ) mainly bound to its <dna>3 ' portion</dna> and bound to the <dna>Sp binding motifs</dna> as well .


In Jurkat T cells , induction of PIF DNA binding activity was rapidly induced , required de novo protein synthesis , and was sustained at a high level for at least 23 h .

In <cell_line>Jurkat T cells</cell_line> , induction of <protein>PIF</protein> DNA binding activity was rapidly induced , required de novo protein synthesis , and was sustained at a high level for at least 23 h .


Interestingly , PIF was constitutively activated in human T-cell leukemia virus type 1-transformed MT-2 cells .

Interestingly , <protein>PIF</protein> was constitutively activated in <cell_line>human T-cell leukemia virus type 1-transformed MT-2 cells</cell_line> .


In this paper , we demonstrate that PIF is Egr-1 based on its recognition by anti- Egr-1 antisera in gel mobility shift assays , even though the IL-2Rbeta DNA binding motif differed substantially from the canonical Egr-1 binding site .

In this paper , we demonstrate that <protein>PIF</protein> is <protein>Egr-1</protein> based on its recognition by anti- <protein>Egr-1</protein> antisera in gel mobility shift assays , even though the <dna>IL-2Rbeta DNA binding motif</dna> differed substantially from the canonical <dna>Egr-1 binding site</dna> .


In addition , Egr-1 bound to the Sp binding site .

In addition , <protein>Egr-1</protein> bound to the <dna>Sp binding site</dna> .


In Jurkat cells , both sites were required for maximal IL-2Rbeta promoter activity , and in HeLaS3 cells , transfection of Egr-1 could drive activity of a reporter construct containing both sites .

In <cell_line>Jurkat cells</cell_line> , both sites were required for maximal <protein>IL-2Rbeta</protein> promoter activity , and in HeLaS3 cells , transfection of <protein>Egr-1</protein> could drive activity of a reporter construct containing both sites .


Moreover , Sp1 and Egr-1 could form a complex with kinetics that correlated with the production of Egr-1 in Jurkat cells upon PMA stimulation .

Moreover , <protein>Sp1</protein> and <protein>Egr-1</protein> could form a complex with kinetics that correlated with the production of <protein>Egr-1</protein> in <cell_line>Jurkat cells</cell_line> upon PMA stimulation .


Thus , Sp1 and Egr-1 physically and functionally cooperate to mediate maximal IL-2Rbeta promoter activity .

Thus , <protein>Sp1</protein> and <protein>Egr-1</protein> physically and functionally cooperate to mediate maximal <dna>IL-2Rbeta promoter</dna> activity .


Overexpression of HSF2-beta inhibits hemin -induced heat shock gene expression and erythroid differentiation in K562 cells .

Overexpression of <protein>HSF2-beta</protein> inhibits <protein>hemin</protein> -induced heat shock gene expression and erythroid differentiation in <cell_line>K562 cells</cell_line> .


Acquisition of heat shock factor 2 ( HSF2 ) DNA binding activity is accompanied by induced transcription of heat shock genes in hemin-treated K562 cells undergoing erythroid differentiation .

Acquisition of heat shock factor 2 ( HSF2 ) DNA binding activity is accompanied by induced transcription of <dna>heat shock genes</dna> in hemin-treated <cell_line>K562 cells</cell_line> undergoing erythroid differentiation .


Previous studies revealed that HSF2 consists of two alternatively spliced isoforms , HSF2-alpha and HSF2-beta , whose relative abundance is developmentally regulated and varies between different tissues .

Previous studies revealed that <protein>HSF2</protein> consists of two alternatively spliced isoforms , <protein>HSF2-alpha</protein> and <protein>HSF2-beta</protein> , whose relative abundance is developmentally regulated and varies between different tissues .


To investigate whether the molar ratio of HSF2-alpha and HSF2-beta isoforms is crucial for the activation of HSF2 and whether the HSF2 isoforms play functionally distinct roles during the hemin-mediated erythroid differentiation , we generated cell clones expressing different levels of HSF2-alpha and HSF2-beta .

To investigate whether the molar ratio of <protein>HSF2-alpha</protein> and <protein>HSF2-beta</protein> isoforms is crucial for the activation of <protein>HSF2</protein> and whether the <protein>HSF2</protein> isoforms play functionally distinct roles during the hemin-mediated erythroid differentiation , we generated cell clones expressing different levels of <protein>HSF2-alpha</protein> and <protein>HSF2-beta</protein> .


We show that in parental K562 cells , the HSF2-alpha isoform is predominantly expressed and HSF2 can be activated upon hemin treatment .

We show that in parental <cell_line>K562 cells</cell_line> , the <protein>HSF2-alpha isoform</protein> is predominantly expressed and <protein>HSF2</protein> can be activated upon hemin treatment .


In contrast , when HSF2-beta is expressed at levels exceeding those of endogenous HSF2-alpha , the hemin-induced DNA binding activity and transcription of heat shock genes are repressed , whereas overexpression of HSF2-alpha results in an enhanced hemin response .

In contrast , when <protein>HSF2-beta</protein> is expressed at levels exceeding those of <protein>endogenous HSF2-alpha</protein> , the hemin-induced DNA binding activity and transcription of <dna>heat shock genes</dna> are repressed , whereas overexpression of <protein>HSF2-alpha</protein> results in an enhanced <protein>hemin</protein> response .


Furthermore , the hemin -induced accumulation of globin , known as a marker of erythroid differentiation , is decreased in cells overexpressing HSF2-beta .

Furthermore , the <protein>hemin</protein> -induced accumulation of <protein>globin</protein> , known as a marker of erythroid differentiation , is decreased in cells overexpressing <protein>HSF2-beta</protein> .


We suggest that HSF2-beta acts as a negative regulator of HSF2 activity during hemin-mediated erythroid differentiation of K562 cells .

We suggest that <protein>HSF2-beta</protein> acts as a negative regulator of <protein>HSF2</protein> activity during hemin-mediated erythroid differentiation of <cell_line>K562 cells</cell_line> .


Sequential development of structural and functional alterations in T cells from tumor-bearing mice .

Sequential development of structural and functional alterations in <cell_type>T cells</cell_type> from tumor-bearing mice .


The TCR alpha beta or -gamma delta chains bind the peptide ligand , whereas the associated CD3 delta epsilon gamma and TCR zeta subunits couple the TCR to intracellular signal transduction components .

The <protein>TCR alpha beta or -gamma delta chains</protein> bind the peptide ligand , whereas the associated <protein>CD3 delta epsilon gamma</protein> and <protein>TCR zeta subunits</protein> couple the <protein>TCR</protein> to intracellular signal transduction components .


Recently , several groups have described marked alterations in signal transduction elements in T cells from cancer patients or in mice bearing tumor for a few weeks ( > 26 days ) .

Recently , several groups have described marked alterations in signal transduction elements in <cell_type>T cells</cell_type> from cancer patients or in mice bearing tumor for a few weeks ( > 26 days ) .


The sequence in which these alterations develop is unknown .


The aim of this study was to explore the kinetics of the development of alterations in signal transduction molecules ( TCR zeta chain , NF kappaB family proteins , and tyrosine kinase p56 ( lck ) ) in mice bearing MC38 colon adenocarcinoma .

The aim of this study was to explore the kinetics of the development of alterations in signal transduction molecules ( <protein>TCR zeta chain</protein> , <protein>NF kappaB family proteins</protein> , and <protein>tyrosine kinase p56 ( lck )</protein> ) in mice bearing MC38 colon adenocarcinoma .


The results demonstrate that alterations in NF kappaB family proteins , specifically the failure of p65 translocation to the nucleus , occur earlier and more frequently than the decrease in zeta-chain .

The results demonstrate that alterations in <protein>NF kappaB family proteins</protein> , specifically the failure of <protein>p65</protein> translocation to the nucleus , occur earlier and more frequently than the decrease in <protein>zeta-chain</protein> .


These defects are paralleled by an impaired ability to produce Th1 cytokines ( IL-2 and IFN-gamma ) .

These defects are paralleled by an impaired ability to produce <protein>Th1 cytokines</protein> ( <protein>IL-2</protein> and <protein>IFN-gamma</protein> ) .


These initial changes are followed by the eventual loss of TCR zeta chain and p56 ( lck ) and a marked decrease in cytotoxic function .

These initial changes are followed by the eventual loss of <protein>TCR zeta chain</protein> and <protein>p56 ( lck )</protein> and a marked decrease in cytotoxic function .


An increased rate of lysosomal degradation is one of the mechanisms responsible for the loss of zeta-chain .

An increased rate of lysosomal degradation is one of the mechanisms responsible for the loss of <protein>zeta-chain</protein> .


HLA-DMA and HLA-DMB gene expression functions through the conserved S-X-Y region .

HLA-DMA and HLA-DMB gene expression functions through the conserved <dna>S-X-Y region</dna> .


The MHC class II homologous proteins HLA-DMA and HLA-DMB function in the loading of peptides onto class II molecules .

The <protein>MHC class II homologous proteins</protein> <protein>HLA-DMA</protein> and <protein>HLA-DMB</protein> function in the loading of peptides onto <protein>class II molecules</protein> .


Like the class II genes , the HLA-DM genes contain upstream regulatory sequences similar to the S-X-Y regulatory region as well as additional putative regulatory sites .

Like the <dna>class II genes</dna> , the <dna>HLA-DM genes</dna> contain upstream regulatory sequences similar to the <dna>S-X-Y regulatory region</dna> as well as additional putative regulatory sites .


To determine whether the DM genes are regulated in a similar manner as class II genes , a series of in vivo and in vitro analyses was performed .

To determine whether the <dna>DM genes</dna> are regulated in a similar manner as <dna>class II genes</dna> , a series of in vivo and in vitro analyses was performed .


Deletion analysis showed that expression from the DM promoters is dependent on the conserved S-X-Y region .

Deletion analysis showed that expression from the <dna>DM promoters</dna> is dependent on the conserved <dna>S-X-Y region</dna> .


The class II-specific transcription factors RFX and CIITA are also required for expression , as cell lines deficient in these factors failed to allow transcription from the DM promoters .

The <protein>class II-specific transcription factors</protein> <protein>RFX</protein> and <protein>CIITA</protein> are also required for expression , as cell lines deficient in these factors failed to allow transcription from the <dna>DM promoters</dna> .


In addition , in vivo footprint analysis showed the putative X and Y boxes to be occupied by transcription factors in wild-type B cells , but not in RFX-deficient B cells .

In addition , in vivo footprint analysis showed the putative <dna>X and Y boxes</dna> to be occupied by <protein>transcription factors</protein> in <cell_type>wild-type B cells</cell_type> , but not in <cell_line>RFX-deficient B cells</cell_line> .


In astrocytes , IFN-gamma treatment induced increased occupancy of these sites .

In <cell_type>astrocytes</cell_type> , <protein>IFN-gamma</protein> treatment induced increased occupancy of these sites .


of the other putative regulatory sites was occupied in vivo , indicating that they may not be functional .


Finally , gel shift analysis showed synergistic complex formation between proteins that bind to the putative X boxes of the DM genes , as is found for the DRA gene .

Finally , gel shift analysis showed synergistic complex formation between proteins that bind to the putative <dna>X boxes</dna> of the DM genes , as is found for the <dna>DRA gene</dna> .


Therefore , the DM genes share a common mechanism of regulation with the class II genes .

Therefore , the <dna>DM genes</dna> share a common mechanism of regulation with the <dna>class II genes</dna> .


Effect of adenovirus 2 on cellular gene activation in blood-derived monocytes and macrophages .

Effect of adenovirus 2 on cellular gene activation in <cell_type>blood-derived monocytes</cell_type> and <cell_type>macrophages</cell_type> .


We have investigated the effect of adenovirus 2 ( Ad2 ) infection on human monocytes and monocyte-derived macrophages with regard to expression of TNF-alpha and IL-1 beta .

We have investigated the effect of adenovirus 2 ( Ad2 ) infection on <cell_type>human monocytes</cell_type> and <cell_type>monocyte-derived macrophages</cell_type> with regard to expression of <protein>TNF-alpha</protein> and <protein>IL-1 beta</protein> .


In monocytes , the virus was bound to the surface without being internalized .


On the other hand , Ad2 was internalized by macrophages .

On the other hand , Ad2 was internalized by <cell_type>macrophages</cell_type> .


No virus replication and no transcription of the Ad2 early genes was observed in either of the cells .

No virus replication and no transcription of the <dna>Ad2 early genes</dna> was observed in either of the cells .


Ad2 infection induced transient increase in the mRNA levels for TNF-alpha and IL-1 beta in both monocytes and in macrophages , although the kinetics of the transcription was slightly different .

Ad2 infection induced transient increase in the <rna>mRNA</rna> levels for <protein>TNF-alpha</protein> and <protein>IL-1 beta</protein> in both <cell_type>monocytes</cell_type> and in <cell_type>macrophages</cell_type> , although the kinetics of the transcription was slightly different .


The production of both cytokines , measured by ELISA tests , was enhanced in monocytes .

The production of both <protein>cytokines</protein> , measured by ELISA tests , was enhanced in <cell_type>monocytes</cell_type> .


In macrophages , a slight enhancement of TNF-alpha production was seen , whereas IL-1 beta was not detected .

In <cell_type>macrophages</cell_type> , a slight enhancement of <protein>TNF-alpha</protein> production was seen , whereas <protein>IL-1 beta</protein> was not detected .


The data indicate that cellular genes might be activated by Ad2 virus infection in nonpermissive cells where no viral gene products could be detected .

The data indicate that <dna>cellular genes</dna> might be activated by Ad2 virus infection in nonpermissive cells where no <protein>viral gene products</protein> could be detected .


Structure and function analysis of the human myeloid cell nuclear differentiation antigen promoter : evidence for the role of Sp1 and not of c-Myb or PU.1 in myelomonocytic lineage-specific expression .

Structure and function analysis of the <dna>human myeloid cell nuclear differentiation antigen promoter</dna> : evidence for the role of <protein>Sp1</protein> and not of <protein>c-Myb</protein> or <protein>PU.1</protein> in myelomonocytic lineage-specific expression .


The human myeloid nuclear differentiation antigen ( MNDA ) is expressed specifically in maturing cells of the myelomonocytic lineage and in monocytes and granulocytes .

The <protein>human myeloid nuclear differentiation antigen</protein> ( <protein>MNDA</protein> ) is expressed specifically in <cell_type>maturing cells</cell_type> of the myelomonocytic lineage and in <cell_type>monocytes</cell_type> and <cell_type>granulocytes</cell_type> .


Epitope enhancement was used to confirm the strict lineage- and stage-specific expression of MNDA in bone marrow as well as in other paraffin-embedded fixed tissues .

Epitope enhancement was used to confirm the strict lineage- and stage-specific expression of <protein>MNDA</protein> in bone marrow as well as in other paraffin-embedded fixed tissues .


A 1-kb region of the gene that includes 5 ' flanking sequence was reported earlier to contain functional promoter activity and was specifically demethylated in expressing cells in contrast to null cells .

A <dna>1-kb region</dna> of the gene that includes <dna>5 ' flanking sequence</dna> was reported earlier to contain functional promoter activity and was specifically demethylated in <cell_type>expressing cells</cell_type> in contrast to <cell_type>null cells</cell_type> .


Further analysis has revealed that this 1-kb fragment promotes higher reporter gene activity in MNDA -expressing cells than non-expressing cells , indicating cell-specific differences in transactivation .

Further analysis has revealed that this <dna>1-kb fragment</dna> promotes higher reporter gene activity in <protein>MNDA</protein> <cell_type>-expressing cells</cell_type> than <cell_type>non-expressing cells</cell_type> , indicating cell-specific differences in transactivation .


This sequence contains consensus elements consistent with myeloid-specific gene expression , including a PU.1 consensus site near the major transcription start site and a cluster of c-Myb sites located several hundred bases upstream of this region .

This sequence contains <dna>consensus elements</dna> consistent with myeloid-specific gene expression , including a <dna>PU.1 consensus site</dna> near the major <dna>transcription start site</dna> and a cluster of <dna>c-Myb sites</dna> located several hundred bases upstream of this region .


However , analysis of deletion mutants localized nearly all of the promoter activity to a short region ( -73 to -16 ) that did not include the cluster of c-Myb sites .

However , analysis of <dna>deletion mutants</dna> localized nearly all of the promoter activity to a short region ( <dna>-73 to -16</dna> ) that did not include the cluster of <dna>c-Myb sites</dna> .


A 4-bp mutation of the core Sp1 consensus element ( GC box ) ( -20 ) reduced overall promoter activity of the 1-kb fragment .

A 4-bp mutation of the <dna>core Sp1 consensus element</dna> ( <dna>GC box</dna> ) ( -20 ) reduced overall promoter activity of the <dna>1-kb fragment</dna> .


Mutation of the PU.1 site did not significantly affect promoter activity .

Mutation of the <dna>PU.1 site</dna> did not significantly affect promoter activity .


Only a small region ( -35 to +22 ) including the Sp1 element and transcription start site , but not the PU.1 site was footprinted .

Only a small region ( -35 to +22 ) including the <dna>Sp1 element</dna> and <dna>transcription start site</dna> , but not the <dna>PU.1 site</dna> was footprinted .


The 4-bp mutation of the core Sp1 consensus element abolished footprinting at the site and an antibody super-shift reaction showed that Sp1 is one of the factors binding the consensus site .

The 4-bp mutation of the core <dna>Sp1 consensus element</dna> abolished footprinting at the site and an antibody super-shift reaction showed that <protein>Sp1</protein> is one of the factors binding the <dna>consensus site</dna> .


The Sp1 site also co-localizes with a DNase I hypersensitive site .

The <dna>Sp1 site</dna> also co-localizes with a <dna>DNase I hypersensitive site</dna> .


The results indicate that DNA methylation , chromatin structure , and transactivation at an Sp1 site contribute to the highly restricted expression of this myelomonocytic lineage specific gene .

The results indicate that DNA methylation , <dna>chromatin</dna> structure , and transactivation at an <dna>Sp1 site</dna> contribute to the highly restricted expression of this <dna>myelomonocytic lineage specific gene</dna> .


Critical cytoplasmic domains of human interleukin-9 receptor alpha chain in interleukin -9-mediated cell proliferation and signal transduction .

Critical <protein>cytoplasmic domains</protein> of <protein>human interleukin-9 receptor alpha chain</protein> in <protein>interleukin</protein> -9-mediated cell proliferation and signal transduction .


Interleukin-9 receptor ( IL-9R ) complex consists of a ligand-specific alpha chain and IL-2R gamma chain .

<protein>Interleukin-9 receptor ( IL-9R ) complex</protein> consists of a <protein>ligand-specific alpha chain</protein> and <protein>IL-2R gamma chain</protein> .


In this study , two regions in the cytoplasmic domain of human IL-9Ralpha were found to be important for IL-9 -mediated cell growth .

In this study , two regions in the <protein>cytoplasmic domain</protein> of <protein>human IL-9Ralpha</protein> were found to be important for <protein>IL-9</protein> -mediated cell growth .


A membrane-proximal region that contains the BOX1 consensus sequence is required for IL-9 -induced cell proliferation and tyrosine phosphorylation of Janus kinases ( JAKs ) .

A <protein>membrane-proximal region</protein> that contains the <protein>BOX1 consensus sequence</protein> is required for <protein>IL-9</protein> -induced cell proliferation and tyrosine phosphorylation of <protein>Janus kinases</protein> ( <protein>JAKs</protein> ) .


Deletion of this region or internal deletion of the BOX1 motif abrogated IL-9 -induced cell proliferation and signal transduction .

Deletion of this region or internal deletion of the <protein>BOX1 motif</protein> abrogated <protein>IL-9</protein> -induced cell proliferation and signal transduction .


However , substitution of the Pro-X-Pro in the BOX1 motif with Ala-X-Ala failed to abolish IL-9 -induced cell proliferation but decreased IL-9 -mediated tyrosine phosphorylation of JAK kinases , insulin receptor substrate-2 , and signal transducer and activator of transcription 3 ( STAT3 ) and expression of c-myc and junB .

However , substitution of the <protein>Pro-X-Pro</protein> in the <protein>BOX1 motif</protein> with <protein>Ala-X-Ala</protein> failed to abolish <protein>IL-9</protein> -induced cell proliferation but decreased <protein>IL-9</protein> -mediated tyrosine phosphorylation of <protein>JAK kinases</protein> , <protein>insulin receptor substrate-2</protein> , and <protein>signal transducer and activator of transcription 3</protein> ( <protein>STAT3</protein> ) and expression of <dna>c-myc</dna> and <dna>junB</dna> .


Another important region is downstream of the BOX1 motif and contains a STAT3 binding motif YLPQ .

Another important region is downstream of the <protein>BOX1 motif</protein> and contains a <dna>STAT3 binding motif</dna> <dna>YLPQ</dna> .


Deletion of this region significantly impaired IL-9 -induced cell growth , activation of JAK kinases , insulin receptor substrate-2 , and STAT3 and expression of early response genes .

Deletion of this region significantly impaired <protein>IL-9</protein> -induced cell growth , activation of <protein>JAK kinases</protein> , <protein>insulin receptor substrate-2</protein> , and <protein>STAT3</protein> and expression of <dna>early response genes</dna> .


A point mutation changing YLPQ into YLPA greatly reduced IL-9 -induced activation of STAT3 and expression of c-myc but did not affect cell proliferation .

A point mutation changing <dna>YLPQ</dna> into <dna>YLPA</dna> greatly reduced <protein>IL-9</protein> -induced activation of <protein>STAT3</protein> and expression of <dna>c-myc</dna> but did not affect cell proliferation .


These results suggest that cooperation or cross-talk of signaling molecules associated with different domains of IL-9Ralpha other than STAT3 is essential for IL-9 -mediated cell growth .

These results suggest that cooperation or cross-talk of signaling molecules associated with different domains of <protein>IL-9Ralpha</protein> other than <protein>STAT3</protein> is essential for <protein>IL-9</protein> -mediated cell growth .


Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells .

<protein>Bcl-2 protein</protein> inhibits bufalin-induced apoptosis through inhibition of <protein>mitogen-activated protein kinase</protein> activation in <cell_line>human leukemia U937 cells</cell_line> .


In a previous study , we demonstrated that bufalin , which is an active principle of Chinese medicine , chan'su , caused apoptosis in human leukemia U937 cells by anomalous activation of mitogen-activated protein kinase ( MAPK ) via the signaling pathway of Ras , Raf-1 , and MAPK kinase-1 .

In a previous study , we demonstrated that bufalin , which is an active principle of Chinese medicine , chan'su , caused apoptosis in <cell_line>human leukemia U937 cells</cell_line> by anomalous activation of <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) via the signaling pathway of <protein>Ras</protein> , <protein>Raf-1</protein> , and <protein>MAPK kinase-1</protein> .


Here , we report the effect of overexpression of bcl-2 in U937 cells on the signaling pathway of apoptosis that is induced by bufalin .

Here , we report the effect of overexpression of <protein>bcl-2</protein> in <cell_line>U937 cells</cell_line> on the signaling pathway of apoptosis that is induced by bufalin .


The results indicated that the apoptosis induced by bufalin in U937 cells was significantly inhibited by overexpression of the Bcl-2 protein .

The results indicated that the apoptosis induced by bufalin in <cell_line>U937 cells</cell_line> was significantly inhibited by overexpression of the <protein>Bcl-2 protein</protein> .


No significant difference was detected in the activation of MAPK kinase-1 that is induced by bufalin in wild-type or Bcl-2-overexpressed U937 cells ; however , the activation of MAPK by bufalin was significantly attenuated in the cells overexpressing Bcl-2 .

No significant difference was detected in the activation of <protein>MAPK kinase-1</protein> that is induced by bufalin in wild-type or <cell_type>Bcl-2-overexpressed U937 cells</cell_type> ; however , the activation of <protein>MAPK</protein> by bufalin was significantly attenuated in the cells overexpressing <protein>Bcl-2</protein> .


Bufalin treatment activated activator protein-1 transcriptional activity ; however , this activation was decreased to 40 % in bcl-2 -overexpressed U937 cells .

Bufalin treatment <protein>activated activator protein-1</protein> transcriptional activity ; however , this activation was decreased to 40 % in <protein>bcl-2</protein> -overexpressed <cell_line>U937 cells</cell_line> .


These results indicate that Bcl-2 acts downstream of MAPK kinase-1 but upstream of MAPK and suggest that , in the signaling pathway of the apoptotic process induced by bufalin , the transcriptional activity of activator protein-1 may be down-regulated through the inhibition of MAPK activity by Bcl-2 .

These results indicate that <protein>Bcl-2</protein> acts downstream of <protein>MAPK kinase-1</protein> but upstream of <protein>MAPK</protein> and suggest that , in the signaling pathway of the apoptotic process induced by bufalin , the transcriptional activity of <protein>activator protein-1</protein> may be down-regulated through the inhibition of <protein>MAPK</protein> activity by <protein>Bcl-2</protein> .


Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding hepatocyte nuclear factor-3alpha , -3beta , -3gamma , -4gamma , and -6 .

Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding <protein>hepatocyte nuclear factor-3alpha , -3beta , -3gamma , -4gamma , and -6</protein> .


The genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function .

The genes encoding the functionally related <protein>hepatocyte nuclear factors</protein> <protein>HNF-1alpha</protein> and <protein>HNF-4alpha</protein> play a critical role in normal pancreatic beta-cell function .


Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes ( maturity-onset diabetes of the young [ MODY ] ) , MODY3 and MODY1 , which are characterized by impaired glucose-stimulated insulin secretion , early disease onset , and autosomal dominant inheritance .

Mutations in these <protein>liver-enriched transcription factors</protein> result in two forms of early-onset type 2 diabetes ( maturity-onset diabetes of the young [ MODY ] ) , MODY3 and MODY1 , which are characterized by impaired glucose-stimulated insulin secretion , early disease onset , and autosomal dominant inheritance .


The transcriptional hierarchy of HNFs suggests that other proteins of the regulatory cascade might be responsible for other forms of MODY and/or late-onset type 2 diabetes .


In this study , we show that HNF-3alpha , -3beta , -3gamma , -4gamma , and -6 are expressed in pancreatic beta-cells .

In this study , we show that <protein>HNF-3alpha , -3beta , -3gamma , -4gamma , and -6</protein> are expressed in <cell_type>pancreatic beta-cells</cell_type> .


We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha , -3beta , -3gamma , -4gamma , and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization .

We report the identification and characterization of <dna>simple tandem repeat DNA polymorphisms</dna> in the genes encoding <protein>HNF-3alpha</protein> , <protein>-3beta</protein> , <protein>-3gamma</protein> , <protein>-4gamma</protein> , and <protein>-6</protein> and the mapping of <protein>HNF-6</protein> to <dna>chromosome bands</dna> <dna>15q21.1-21.2</dna> by fluorescence in situ hybridization .


These markers will be useful to study the role of genetic variation in these genes in the pathogenesis of type 2 diabetes .


Induction of nuclear factor kappa B/Rel nuclear activity in human peripheral blood T lymphocytes by anti-HLA class I monoclonal antibodies .

Induction of <protein>nuclear factor kappa B/Rel</protein> nuclear activity in <cell_type>human peripheral blood T lymphocytes</cell_type> by <protein>anti-HLA class I monoclonal antibodies</protein> .


Monoclonal antibodies against either monomorphic or polymorphic determinants of class I antigen induced in PBMC and highly purified T lymphocytes the nuclear activity of NF-kappa B/Rel complexes .

Monoclonal antibodies against either monomorphic or polymorphic determinants of <protein>class I antigen</protein> induced in <cell_type>PBMC</cell_type> and highly <cell_type>purified T lymphocytes</cell_type> the nuclear activity of <protein>NF-kappa B/Rel complexes</protein> .


These included both p50/p50 and p50/p65 dimers , recognized by specific antibodies in EMSA .

These included both <protein>p50/p50</protein> and <protein>p50/p65 dimers</protein> , recognized by <protein>specific antibodies</protein> in EMSA .


The induced complexes were detectable in extracts of cells incubated with anti-class I monoclonal antibody ( mAb ) for 1.5 h ; the induction was maximal at 5 h , persistent at 16 h and no longer observed at 40 h .

The induced <protein>complexes</protein> were detectable in extracts of cells incubated with <protein>anti-class I monoclonal antibody</protein> ( <protein>mAb</protein> ) for 1.5 h ; the induction was maximal at 5 h , persistent at 16 h and no longer observed at 40 h .


The mAb failed to induce NF-kappa B/Rel nuclear activity in cells incubated in the presence of 3 , 4-dichloroisocoumarin , an inhibitor of I kappa B-alpha degradation .

The <protein>mAb</protein> failed to induce <protein>NF-kappa B/Rel</protein> nuclear activity in cells incubated in the presence of 3 , 4-dichloroisocoumarin , an inhibitor of <protein>I kappa B-alpha</protein> degradation .


Together , these results suggest that class I triggering can induce the activity of NF-kappa B/Rel nuclear activity in peripheral blood T lymphocytes , thereby modulating the expression of genes regulated by these transcription factors .

Together , these results suggest that class I triggering can induce the activity of <protein>NF-kappa B/Rel</protein> nuclear activity in <cell_type>peripheral blood T lymphocytes</cell_type> , thereby modulating the expression of genes regulated by these <protein>transcription factors</protein> .


Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces potent proinflammatory cytokine mRNA expression in human monocytes through sustained reduction of IkappaB-alpha and activation of NF-kappaB .

<protein>Anti-Ehrlichia chaffeensis antibody</protein> complexed with E. chaffeensis induces potent <rna>proinflammatory cytokine mRNA</rna> expression in <cell_type>human monocytes</cell_type> through sustained reduction of <protein>IkappaB-alpha</protein> and activation of <protein>NF-kappaB</protein> .


Ehrlichia chaffeensis is an obligatory intracellular bacterium that infects monocytes and macrophages and is the etiologic agent of human ehrlichiosis in the United States .

Ehrlichia chaffeensis is an obligatory intracellular bacterium that infects <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> and is the etiologic agent of human ehrlichiosis in the United States .


Our previous studies showed that the exposure of human monocytes to E. chaffeensis induces the expression of interleukin-1beta ( IL-1beta ) , IL-8 , and IL-10 genes in vitro but not the expression of tumor necrosis factor alpha ( TNF-alpha ) and IL-6 mRNAs .

Our previous studies showed that the exposure of <cell_type>human monocytes</cell_type> to E. chaffeensis induces the expression of <protein>interleukin-1beta</protein> ( <protein>IL-1beta</protein> ) , <protein>IL-8</protein> , and <dna>IL-10 genes</dna> in vitro but not the expression of <rna>tumor necrosis factor alpha ( TNF-alpha ) and IL-6 mRNAs</rna> .


In this study , the effect of anti-E. chaffeensis antibody complexed with E. chaffeensis on the expression of major proinflammatory cytokines in human monocytes was examined .

In this study , the effect of <protein>anti-E. chaffeensis antibody</protein> complexed with E. chaffeensis on the expression of <protein>major proinflammatory cytokines</protein> in <cell_type>human monocytes</cell_type> was examined .


Human monocytic cell line THP-1 was treated with E. chaffeensis which had been preincubated with human anti-E. chaffeensis serum for 2 h , and the levels of cytokine mRNAs were evaluated by competitive reverse transcription-PCR .

<cell_line>Human monocytic cell line THP-1</cell_line> was treated with E. chaffeensis which had been preincubated with human anti-E. chaffeensis serum for 2 h , and the levels of <rna>cytokine mRNAs</rna> were evaluated by competitive reverse transcription-PCR .


Anti-E. chaffeensis antibody complexed with E. chaffeensis significantly enhanced mRNA expression of IL-1beta in THP-1 cells .

<protein>Anti-E. chaffeensis antibody</protein> complexed with E. chaffeensis significantly enhanced mRNA expression of <protein>IL-1beta</protein> in <cell_line>THP-1 cells</cell_line> .


The expression of TNF-alpha and IL-6 mRNAs was also induced .

The expression of <rna>TNF-alpha and IL-6 mRNAs</rna> was also induced .