IFN-alpha enhanced tyrosine phosphorylation of STAT1 , STAT3 , STAT4 , STAT5a , and STAT5b .

<protein>IFN-alpha</protein> enhanced tyrosine phosphorylation of STAT1 , <protein>STAT3</protein> , <protein>STAT4</protein> , <protein>STAT5a</protein> , and <protein>STAT5b</protein> .


IL-12 induced STAT4 and IL-2 and IL-15 induced STAT5 binding to the GAS elements .

<protein>IL-12</protein> induced <protein>STAT4</protein> and <protein>IL-2</protein> and <protein>IL-15</protein> induced <protein>STAT5</protein> binding to the <dna>GAS elements</dna> .


Taken together , our results suggest that IFN-alpha , IL-2 , IL-12 , and IL-15 have overlapping activities on human T cells .

Taken together , our results suggest that <protein>IFN-alpha</protein> , <protein>IL-2</protein> , <protein>IL-12</protein> , and <protein>IL-15</protein> have overlapping activities on <cell_type>human T cells</cell_type> .


These findings thus emphasize the importance of IFN-alpha as a T-cell regulatory cytokine .

These findings thus emphasize the importance of <protein>IFN-alpha</protein> as a <protein>T-cell regulatory cytokine</protein> .


The Megakaryocyte/Platelet-specific enhancer of the alpha2beta1 integrin gene : two tandem AP1 sites and the mitogen-activated protein kinase signaling cascade .

The <dna>Megakaryocyte/Platelet-specific enhancer</dna> of the <dna>alpha2beta1 integrin gene</dna> : two tandem <dna>AP1 sites</dna> and the <protein>mitogen-activated protein kinase</protein> signaling cascade .


The alpha2beta1 integrin , a collagen receptor on platelets and megakaryocytes , is required for normal platelet function .

The <protein>alpha2beta1 integrin</protein> , a collagen receptor on <cell_type>platelets</cell_type> and <cell_type>megakaryocytes</cell_type> , is required for normal platelet function .


Transcriptional regulation of the alpha2 integrin gene in cells undergoing megakaryocytic differentiation requires a core promoter between bp -30 and -92 , a silencer between bp -92 and -351 , and megakaryocytic enhancers in the distal 5 ' flank .

Transcriptional regulation of the <dna>alpha2 integrin gene</dna> in cells undergoing megakaryocytic differentiation requires a <dna>core promoter</dna> between bp -30 and -92 , a <dna>silencer</dna> between bp -92 and -351 , and <dna>megakaryocytic enhancers</dna> in the <dna>distal 5 ' flank</dna> .


We have now identified a 229-bp region of the distal 5 ' flank of the alpha2 integrin gene required for high-level enhancer activity in cells with megakaryocytic features .

We have now identified a <dna>229-bp region</dna> of the <dna>distal 5 ' flank</dna> of the <dna>alpha2 integrin gene</dna> required for <cell_type>high-level enhancer activity in cells</cell_type> with megakaryocytic features .


Two tandem AP1 binding sites with dyad symmetry are required for enhancer activity and for DNA-protein complex formation with members of the c-fos/c-jun family .

Two tandem <dna>AP1 binding sites</dna> with dyad symmetry are required for enhancer activity and for <protein>DNA-protein complex</protein> formation with members of the <protein>c-fos/c-jun family</protein> .


The requirement for AP1 activation suggested a role for the mitogen-activated protein kinase ( MAPK ) signaling pathway in regulating alpha2 integrin gene expression .

The requirement for <protein>AP1</protein> activation suggested a role for the <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) signaling pathway in regulating <dna>alpha2 integrin gene</dna> expression .


Inhibition of the MAP kinase cascade with PD98059 , a specific inhibitor of MAPK kinase 1 , prevented the expression of the alpha2 integrin subunit in cells induced to become megakaryocytic .

Inhibition of the <protein>MAP kinase</protein> cascade with PD98059 , a specific inhibitor of <protein>MAPK kinase 1</protein> , prevented the expression of the <protein>alpha2 integrin subunit</protein> in cells induced to become megakaryocytic .


We provide a model of megakaryocytic differentiation in which expression of the alpha2 integrin gene requires signaling via the MAP kinase pathway to activate two tandem AP1 binding sites in the alpha2 integrin enhancer .

We provide a model of megakaryocytic differentiation in which expression of the <dna>alpha2 integrin gene</dna> requires signaling via the <protein>MAP kinase</protein> pathway to activate two tandem <dna>AP1 binding sites</dna> in the <dna>alpha2 integrin enhancer</dna> .


Functional association of Nmi with Stat5 and Stat1 in IL-2 -and IFNgamma -mediated signaling .

Functional association of <protein>Nmi</protein> with <protein>Stat5</protein> and <protein>Stat1</protein> in <protein>IL-2</protein> -and <protein>IFNgamma</protein> -mediated signaling .


Using the coiled-coil region of Stat5b as the bait in a yeast two-hybrid screen , we identified the association of Nmi , a protein of unknown function previously reported as an N-Myc interactor .

Using the coiled-coil region of <protein>Stat5b</protein> as the bait in a yeast two-hybrid screen , we identified the association of <protein>Nmi</protein> , a protein of unknown function previously reported as an <protein>N-Myc</protein> interactor .


We further show that Nmi interacts with all STATs except Stat2 .

We further show that <protein>Nmi</protein> interacts with all <protein>STATs</protein> except <protein>Stat2</protein> .


We evaluated two cytokine systems , IL-2 and IFNgamma , and demonstrate that Nmi augments STAT -mediated transcription in response to these cytokines .

We evaluated two cytokine systems , <protein>IL-2</protein> and <protein>IFNgamma</protein> , and demonstrate that <protein>Nmi</protein> augments <protein>STAT</protein> -mediated transcription in response to these <protein>cytokines</protein> .


Interestingly , Nmi lacks an intrinsic transcriptional activation domain ; instead , Nmi enhances the association of CBP/p300 coactivator proteins with Stat1 and Stat5 , and together with CBP/p300 can augment IL-2- and IFNgamma-dependent transcription .

Interestingly , <protein>Nmi</protein> lacks an intrinsic <protein>transcriptional activation domain</protein> ; instead , <protein>Nmi</protein> enhances the association of <protein>CBP/p300 coactivator proteins</protein> with <protein>Stat1</protein> and <protein>Stat5</protein> , and together with <protein>CBP/p300</protein> can augment IL-2- and IFNgamma-dependent transcription .


Therefore , our data not only reveal that Nmi can potentiate STAT -dependent transcription , but also suggest that it can augment coactivator protein recruitment to at least some members of a group of sequence-specific transcription factors .

Therefore , our data not only reveal that <protein>Nmi</protein> can potentiate <protein>STAT</protein> -dependent transcription , but also suggest that it can augment coactivator protein recruitment to at least some members of a group of <protein>sequence-specific transcription factors</protein> .


Lactobacilli and vaginal host defense : activation of the human immunodeficiency virus type 1 long terminal repeat , cytokine production , and NF-kappaB .

Lactobacilli and vaginal host defense : activation of the <dna>human immunodeficiency virus type 1 long terminal repeat</dna> , <protein>cytokine</protein> production , and <protein>NF-kappaB</protein> .


Lactobacilli , a component of the normal vaginal flora , can activate the human immunodeficiency virus ( HIV ) -1 long terminal repeat ( LTR ) in the Jurkat T lymphocyte and THP-1 macrophage cell lines .

Lactobacilli , a component of the normal vaginal flora , can activate the <dna>human immunodeficiency virus ( HIV ) -1 long terminal repeat</dna> ( <dna>LTR</dna> ) in the <cell_line>Jurkat T lymphocyte</cell_line> and <cell_line>THP-1 macrophage cell lines</cell_line> .


Activation of the LTR in Jurkat cells was strongly enhanced by vanadate and inhibited by catalase , implicating H2O2 .

Activation of the <dna>LTR</dna> in <cell_line>Jurkat cells</cell_line> was strongly enhanced by vanadate and inhibited by <protein>catalase</protein> , implicating H2O2 .


In contrast , activation in THP-1 cells occurred in the absence of vanadate and was unaffected by catalase .

In contrast , activation in <protein>THP-1 cells</protein> occurred in the absence of vanadate and was unaffected by <protein>catalase</protein> .


The active material partitioned into the phenol layer on hot aqueous phenol extraction .


Lactobacilli also increased tumor necrosis factor -alphaand interleukin -1betaproduction and activated NF-kappaB in THP-1 cells and increased tumor necrosis factor -alphaproduction by human monocytes .

Lactobacilli also increased <protein>tumor necrosis factor</protein> -alphaand <protein>interleukin</protein> -1betaproduction and activated <protein>NF-kappaB</protein> in <protein>THP-1 cells</protein> and increased <protein>tumor necrosis factor</protein> -alphaproduction by <cell_type>human monocytes</cell_type> .


Human vaginal fluid specimens had comparable properties , which correlated with their bacterial content .


These findings suggest the presence in vaginal fluid of agent ( s ) derived from indigenous bacteria that can activate the HIV-1 LTR , cytokine production , and NF-kappaB in cells of macrophage lineage , with possible influence on vaginal physiology and host defense .

These findings suggest the presence in vaginal fluid of agent ( s ) derived from indigenous bacteria that can activate the <dna>HIV-1 LTR</dna> , <protein>cytokine</protein> production , and <protein>NF-kappaB</protein> in cells of <cell_type>macrophage lineage</cell_type> , with possible influence on vaginal physiology and host defense .


T cell priming enhances IL-4 gene expression by increasing nuclear factor of activated T cells .

T cell priming enhances <dna>IL-4 gene</dna> expression by increasing <protein>nuclear factor of activated T cells</protein> .


The repetitive activation of T cells ( priming ) enhances the expression of many cytokines , such as IL-4 , but not others , such as IL-2 .

The repetitive activation of <cell_type>T cells</cell_type> ( priming ) enhances the expression of many <protein>cytokines</protein> , such as IL-4 , but not others , such as <protein>IL-2</protein> .


Molecular mechanisms underlying selective expression of cytokines by T cells remain poorly understood .

Molecular mechanisms underlying selective expression of <protein>cytokines</protein> by <cell_type>T cells</cell_type> remain poorly understood .


Here we show that priming of CD4 T cells selectively enhances IL-4 expression relative to IL-2 expression by a transcriptional mechanism involving nuclear factor of activated T cells ( NFAT ) proteins .

Here we show that priming of <cell_type>CD4 T cells</cell_type> selectively enhances <protein>IL-4</protein> expression relative to <protein>IL-2</protein> expression by a transcriptional mechanism involving <protein>nuclear factor of activated T cells ( NFAT ) proteins</protein> .


As detected by in vivo footprinting , priming markedly increases the activation-dependent engagement of the P0 and P1 NFAT-binding elements of the IL-4 promoter .

As detected by in vivo footprinting , priming markedly increases the activation-dependent engagement of the <dna>P0</dna> and <dna>P1</dna> <dna>NFAT-binding elements</dna> of the <dna>IL-4 promoter</dna> .


Moreover , each proximal P element is essential for optimal IL-4 promoter activity .

Moreover , each <dna>proximal P element</dna> is essential for optimal <dna>IL-4 promoter</dna> activity .


Activated primed CD4 T cells contain more NFAT1 and support greater NFAT -directed transcription than unprimed CD4 T cells , while activator protein 1 binding and activator protein 1 -mediated transcription by both cell types is similar .

Activated primed <cell_type>CD4 T cells</cell_type> contain more <protein>NFAT1</protein> and support greater <protein>NFAT</protein> -directed transcription than unprimed <cell_type>CD4 T cells</cell_type> , while <protein>activator protein 1</protein> binding and <protein>activator protein 1</protein> -mediated transcription by both cell types is similar .


Increased expression of wild-type NFAT1 substantially increases IL-4 promoter activity in unprimed CD4 T cells , suggesting NFAT1 may be limiting for IL-4 gene expression in this cell type .

Increased expression of wild-type <protein>NFAT1</protein> substantially increases <dna>IL-4 promoter</dna> activity in unprimed <cell_type>CD4 T cells</cell_type> , suggesting <protein>NFAT1</protein> may be limiting for <protein>IL-4</protein> gene expression in this cell type .


Furthermore , a truncated form of NFAT1 acts as a dominant-negative , reducing IL-4 promoter activity in primed CD4 T cells and confirming the importance of endogenous NFAT to increased IL-4 gene expression by effector T cells .

Furthermore , a truncated form of <protein>NFAT1</protein> acts as a dominant-negative , reducing <dna>IL-4 promoter</dna> activity in primed <cell_type>CD4 T cells</cell_type> and confirming the importance of <protein>endogenous NFAT</protein> to increased <protein>IL-4</protein> gene expression by effector T cells .


NFAT1 appears to be the major NFAT family member responsible for the initial increased expression of IL-4 by primed CD4 T cells .

<protein>NFAT1</protein> appears to be the major <protein>NFAT family member</protein> responsible for the initial increased expression of <protein>IL-4</protein> by primed <cell_type>CD4 T cells</cell_type> .


Differential monocyte adhesion and adhesion molecule expression in venous and arterial endothelial cells .

Differential monocyte adhesion and <protein>adhesion molecule</protein> expression in venous and arterial endothelial cells .


We compared U-937 cell adhesion and adhesion molecule expression in human umbilical venous ( HUVECs ) and arterial ( HUAECs ) endothelial cells exposed to tumor necrosis factor ( TNF ) , interleukin-1 , and lipopolysaccharide ( LPS ) .

We compared <cell_line>U-937 cell</cell_line> adhesion and <protein>adhesion molecule</protein> expression in <cell_type>human umbilical venous</cell_type> ( <cell_type>HUVECs</cell_type> ) and <cell_type>arterial ( HUAECs ) endothelial cells</cell_type> exposed to <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) , <protein>interleukin-1</protein> , and lipopolysaccharide ( LPS ) .


TNF and LPS stimulated vascular cell adhesion molecule ( VCAM ) -1 surface expression and adhesion of U-937 monocyte-like cells to HUVECs but not to HUAECs .

<protein>TNF</protein> and LPS stimulated <protein>vascular cell adhesion molecule</protein> ( <protein>VCAM</protein> ) -1 surface expression and adhesion of <cell_line>U-937 monocyte-like cells</cell_line> to <cell_type>HUVECs</cell_type> but not to <cell_type>HUAECs</cell_type> .


Antibody studies demonstrated that in HUVECs at least 75 % of the adhesion response is VCAM-1 mediated .

Antibody studies demonstrated that in <cell_type>HUVECs</cell_type> at least 75 % of the adhesion response is <protein>VCAM-1</protein> mediated .


Interleukin-1 stimulated U-937 cell adhesion to and VCAM-1 surface expression in both HUVECs and HUAECs .

<protein>Interleukin-1</protein> stimulated <cell_line>U-937 cell</cell_line> adhesion to and <protein>VCAM-1</protein> surface expression in both <cell_type>HUVECs</cell_type> and <cell_type>HUAECs</cell_type> .


Pyrrolidinedithiocarbamate and the proteasome inhibitor MG-132 blocked TNF -and LPS-stimulated U-937 cell adhesion to HUVECs .

Pyrrolidinedithiocarbamate and the proteasome inhibitor MG-132 blocked <protein>TNF</protein> -and LPS-stimulated <cell_line>U-937 cell</cell_line> adhesion to <cell_type>HUVECs</cell_type> .


These agents also significantly decreased TNF -and LPS-stimulated increases in HUVEC surface VCAM-1 .

These agents also significantly decreased <protein>TNF</protein> -and LPS-stimulated increases in <protein>HUVEC surface VCAM-1</protein> .


TNF increased VCAM-1 protein and mRNA in HUVECs that was blocked by pyrrolidinedithiocarbamate .

<protein>TNF</protein> increased <protein>VCAM-1</protein> protein and <rna>mRNA</rna> in <cell_type>HUVECs</cell_type> that was blocked by pyrrolidinedithiocarbamate .


However , neither TNF or LPS stimulated VCAM-1 expression in HUAECs .

However , neither <protein>TNF</protein> or LPS stimulated <protein>VCAM-1</protein> expression in <cell_type>HUAECs</cell_type> .


TNF stimulated expression of both intercellular adhesion molecule-1 and E-selectin in HUVECs , but in HUAECs , only intercellular adhesion molecule-1 was increased .

<protein>TNF</protein> stimulated expression of both <protein>intercellular adhesion molecule-1</protein> and <protein>E-selectin</protein> in <cell_type>HUVECs</cell_type> , but in <cell_type>HUAECs</cell_type> , only <protein>intercellular adhesion molecule-1</protein> was increased .


Electrophoretic mobility shift assays demonstrated no difference in the pattern of TNF -stimulated nuclear factor-kappaB activation between HUVECs and HUAECs .

Electrophoretic mobility shift assays demonstrated no difference in the pattern of <protein>TNF</protein> -stimulated <protein>nuclear factor-kappaB</protein> activation between <cell_type>HUVECs</cell_type> and <cell_type>HUAECs</cell_type> .


These studies demonstrate a novel and striking insensitivity of arterial endothelium to the effects of TNF and LPS and indicate a dissociation between the ability of HUAECs to upregulate nuclear factor-kappaB and VCAM-1 .

These studies demonstrate a novel and striking insensitivity of arterial endothelium to the effects of <protein>TNF</protein> and LPS and indicate a dissociation between the ability of <cell_type>HUAECs</cell_type> to upregulate <protein>nuclear factor-kappaB</protein> and <protein>VCAM-1</protein> .


Functional testosterone receptors in plasma membranes of T cells .

Functional <protein>testosterone receptors</protein> in plasma membranes of <cell_type>T cells</cell_type> .


T cells are considered to be unresponsive to testosterone due to the absence of androgen receptors ( AR ) .

<cell_type>T cells</cell_type> are considered to be unresponsive to testosterone due to the absence of <protein>androgen receptors</protein> ( <protein>AR</protein> ) .


Here , we demonstrate the testosterone responsiveness of murine splenic T cells in vitro as well as the presence of unconventional cell surface receptors for testosterone and classical intracellular AR .

Here , we demonstrate the testosterone responsiveness of <cell_type>murine splenic T cells</cell_type> in vitro as well as the presence of <protein>unconventional cell surface receptors</protein> for testosterone and <protein>classical intracellular AR</protein> .


Binding sites for testosterone on the surface of both CD4 ( + ) and CD8 ( + ) subsets of T cells are directly revealed with the impeded ligand testosterone-BSA-FITC by confocal laser scanning microscopy ( CLSM ) and flow cytometry , respectively .

Binding sites for testosterone on the surface of both <cell_type>CD4 ( + ) and CD8 ( + ) subsets</cell_type> of <cell_type>T cells</cell_type> are directly revealed with the impeded ligand testosterone-BSA-FITC by confocal laser scanning microscopy ( CLSM ) and flow cytometry , respectively .


Binding of the plasma membrane impermeable testosterone-BSA conjugate induces a rapid rise ( < 5 s ) in [ Ca2+ ] i of Fura-2-loaded T cells .

Binding of the plasma membrane impermeable <protein>testosterone-BSA conjugate</protein> induces a rapid rise ( < 5 s ) in [ Ca2+ ] i of <cell_type>Fura-2-loaded T cells</cell_type> .


This rise reflects influx of extracellular Ca2+ through non-voltage-gated and Ni2+-blockable Ca2+ channels of the plasma membrane .

This rise reflects influx of extracellular Ca2+ through non-voltage-gated and <protein>Ni2+-blockable Ca2+ channels</protein> of the plasma membrane .


The testosterone-BSA-induced Ca2+ import is not affected by cyproterone , a blocker of the AR .

The testosterone-BSA-induced Ca2+ import is not affected by cyproterone , a blocker of the <protein>AR</protein> .


In addition , AR are not detectable on the surface of intact T cells when using anti-AR antibodies directed against the amino and carboxy terminus of the AR , although T cells contain AR , as revealed by reverse transcription-polymerase chain reactions and Western blotting .

In addition , <protein>AR</protein> are not detectable on the surface of <cell_type>intact T cells</cell_type> when using <protein>anti-AR antibodies</protein> directed against the <protein>amino and carboxy terminus</protein> of the <protein>AR</protein> , although <cell_type>T cells</cell_type> contain <protein>AR</protein> , as revealed by reverse transcription-polymerase chain reactions and Western blotting .


AR can be visualized with the anti-AR antibodies in the cytoplasm of permeabilized T cells by using CLSM , though AR are not detectable in cytosol fractions when using the charcoal binding assay with 3H-R1881 as ligand .

<protein>AR</protein> can be visualized with the <protein>anti-AR antibodies</protein> in the cytoplasm of <cell_type>permeabilized T cells</cell_type> by using CLSM , though <protein>AR</protein> are not detectable in cytosol fractions when using the charcoal binding assay with 3H-R1881 as ligand .


Cytoplasmic AR do not translocate to the nucleus of T cells in the presence of testosterone , in contrast to cytoplasmic AR in human cancer LNCaP cells .

<protein>Cytoplasmic AR</protein> do not translocate to the nucleus of <cell_type>T cells</cell_type> in the presence of testosterone , in contrast to <protein>cytoplasmic AR</protein> in <cell_line>human cancer LNCaP cells</cell_line> .


These findings suggest that the classical AR present in splenic T cells are not active in the genomic pathway .

These findings suggest that the <protein>classical AR</protein> present in <cell_type>splenic T cells</cell_type> are not active in the genomic pathway .


By contrast , the cell surface receptors for testosterone are in a functionally active state , enabling T cells a nongenomic response to testosterone .

By contrast , the <protein>cell surface receptors</protein> for testosterone are in a functionally active state , enabling <cell_type>T cells</cell_type> a nongenomic response to testosterone .


Limited proteolysis for assaying ligand binding affinities of nuclear receptors .

Limited proteolysis for assaying ligand binding affinities of <protein>nuclear receptors</protein> .


The binding of natural or synthetic ligands to nuclear receptors is the triggering event leading to gene transcription activation or repression .

The binding of natural or synthetic ligands to <protein>nuclear receptors</protein> is the triggering event leading to gene transcription activation or repression .


Ligand binding to the ligand binding domain of these receptors induces conformational changes that are evidenced by an increased resistance of this domain to proteases .

Ligand binding to the <protein>ligand binding domain</protein> of these <protein>receptors</protein> induces conformational changes that are evidenced by an increased resistance of this domain to <protein>proteases</protein> .


In vitro labeled receptors were incubated with various synthetic or natural agonists or antagonists and submitted to trypsin digestion .

<protein>In vitro labeled receptors</protein> were incubated with various synthetic or natural agonists or antagonists and submitted to <protein>trypsin</protein> digestion .


Proteolysis products were separated by SDS-PAGE and quantified .


The amount of trypsin -resistant fragments was proportional to receptor occupancy by the ligand , and allowed the determination of dissociation constants ( kDa ) .

The amount of <protein>trypsin</protein> -resistant fragments was proportional to receptor occupancy by the ligand , and allowed the determination of dissociation constants ( kDa ) .


Using the wild-type or mutated human retinoic acid receptor alpha as a model , kDa values determined by classical competition binding assays using tritiated ligands are in agreement with those measured by the proteolytic assay .

Using the <protein>wild-type or mutated human retinoic acid receptor alpha</protein> as a model , kDa values determined by classical competition binding assays using tritiated ligands are in agreement with those measured by the proteolytic assay .


This method was successfully extended to human retinoic X receptor alpha , glucocorticoid receptor , and progesterone receptor , thus providing a basis for a new , faster assay to determine simultaneously the affinity and conformation of receptors when bound to a given ligand .

This method was successfully extended to <protein>human retinoic X receptor alpha</protein> , <protein>glucocorticoid receptor</protein> , and <protein>progesterone receptor</protein> , thus providing a basis for a new , faster assay to determine simultaneously the affinity and conformation of receptors when bound to a given ligand .


Genes that regulate interleukin-4 expression in T cells .

Genes that regulate <protein>interleukin-4</protein> expression in <cell_type>T cells</cell_type> .


Interleukin-4 is an immunomodulatory cytokine which plays a central role in the regulation of allergic and atopic immune responses .

<protein>Interleukin-4</protein> is an <protein>immunomodulatory cytokine</protein> which plays a central role in the regulation of allergic and atopic immune responses .


Significant progress has been made in gaining a detailed understanding of the transcriptional regulation of the interleukin-4 gene .

Significant progress has been made in gaining a detailed understanding of the transcriptional regulation of the <dna>interleukin-4 gene</dna> .


The recent identification and characterization of several key transcription factors has helped to elucidate the molecular mechanisms of T helper cell cytokine gene expression .

The recent identification and characterization of several key <protein>transcription factors</protein> has helped to elucidate the molecular mechanisms of <dna>T helper cell cytokine gene</dna> expression .


B lymphocytes from patients with chronic lymphocytic leukemia contain signal transducer and activator of transcription ( STAT ) 1 and STAT3 constitutively phosphorylated on serine residues .

<cell_type>B lymphocytes</cell_type> from patients with chronic lymphocytic leukemia contain <protein>signal transducer and activator of transcription ( STAT ) 1</protein> and <protein>STAT3</protein> constitutively phosphorylated on serine residues .


To explore the pathogenesis of chronic lymphocytic leukemia ( CLL ) , we examined whether phosphorylation of one or more signal transducer and activator of transcription ( STAT ) factors was abnormal in cells from CLL patients .

To explore the pathogenesis of chronic lymphocytic leukemia ( CLL ) , we examined whether phosphorylation of one or more <protein>signal transducer and activator of transcription ( STAT ) factors</protein> was abnormal in cells from CLL patients .


No constitutive tyrosine phosphorylation was detected on any STAT in CLL cells .

No constitutive tyrosine phosphorylation was detected on any <protein>STAT</protein> in <cell_line>CLL cells</cell_line> .


To assess the phosphorylation of serine residues of STAT1 and STAT3 in CLL cells , we raised antibodies that specifically recognize the form of STAT1 phosphorylated on ser-727 and the form of STAT3 phosphorylated on ser-727 .

To assess the phosphorylation of serine residues of <protein>STAT1</protein> and <protein>STAT3</protein> in <cell_line>CLL cells</cell_line> , we raised antibodies that specifically recognize the form of <protein>STAT1</protein> phosphorylated on ser-727 and the form of <protein>STAT3</protein> phosphorylated on ser-727 .


We found that in 100 % of patients with CLL ( n = 32 ) , STAT1 and STAT3 were constitutively phosphorylated on serine .

We found that in 100 % of patients with CLL ( n = 32 ) , <protein>STAT1</protein> and <protein>STAT3</protein> were constitutively phosphorylated on serine .


This was in contrast to normal peripheral blood B lymphocytes or CD5+ ) B cells isolated from tonsils , in which this phosphorylation was absent .

This was in contrast to normal peripheral blood <cell_type>B lymphocytes</cell_type> or <cell_type>CD5+ ) B cells</cell_type> isolated from tonsils , in which this phosphorylation was absent .


Serine phosphorylation of STAT1 and STAT3 was seen occasionally in other leukemias , but it was a universal finding only in CLL .

Serine phosphorylation of <protein>STAT1</protein> and <protein>STAT3</protein> was seen occasionally in other leukemias , but it was a universal finding only in CLL .


The serine phosphorylation of these STATs was a continuous process , as incubation of CLL cells with the kinase inhibitor H7 led to the dephosphorylation of these serine residues .

The serine phosphorylation of these <protein>STATs</protein> was a continuous process , as incubation of <cell_line>CLL cells</cell_line> with the <protein>kinase inhibitor H7</protein> led to the dephosphorylation of these serine residues .


The STAT serine kinase in CLL cells has not been identified , and appears to be neither mitogen-activated protein kinase nor pp70 ( s6k ) .

The STAT serine kinase in CLL cells has not been identified , and appears to be neither <protein>mitogen-activated protein kinase</protein> nor <protein>pp70 ( s6k )</protein> .


In summary , the constitutive serine phosphorylation of STAT1 and STAT3 is present in all CLL samples tested to date , although the physiologic significance of this modification remains to be determined .

In summary , the constitutive serine phosphorylation of <protein>STAT1</protein> and <protein>STAT3</protein> is present in all CLL samples tested to date , although the physiologic significance of this modification remains to be determined .


Activation of human immunodeficiency virus type 1 expression by Gardnerella vaginalis .


Bacterial vaginosis ( BV ) is associated with an increased rate of sexual transmission of human immunodeficiency virus ( HIV ) type 1 , and Gardnerella vaginalis is frequently isolated from the genital tracts of women with BV .


G. vaginalis lysates were found to significantly stimulate HIV expression in monocytoid cells .

G. vaginalis lysates were found to significantly stimulate HIV expression in <cell_type>monocytoid cells</cell_type> .


Stimulation was significantly higher when lysates were heated at 100 degrees C for 5 min but was reduced by treatment with lysozyme or protease .

Stimulation was significantly higher when lysates were heated at 100 degrees C for 5 min but was reduced by treatment with <protein>lysozyme</protein> or <protein>protease</protein> .


G. vaginalis lysates also activated HIV expression in certain T cell lines .

G. vaginalis lysates also activated HIV expression in certain <cell_line>T cell lines</cell_line> .


G. vaginalis lysates activated HIV long-terminal repeat transcription in HIV-infected cells and increased NF-kappaB binding activity , indicating an effect by G. vaginalis on HIV transcription .

G. vaginalis lysates activated HIV long-terminal repeat transcription in <cell_type>HIV-infected cells</cell_type> and increased <protein>NF-kappaB</protein> binding activity , indicating an effect by G. vaginalis on HIV transcription .


The activation of HIV production by G. vaginalis suggests that genital tract infection with G. vaginalis increases the risk of HIV transmission by increasing HIV expression in the genital tract .


This may explain , at least in part , the increased rate of HIV transmission in women with BV .


Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1 .

<protein>Interleukin-10</protein> inhibits expression of both <dna>interferon alpha- and interferon gamma- induced genes</dna> by suppressing tyrosine phosphorylation of <protein>STAT1</protein> .


Interleukin-10 ( IL-10 ) helps maintain polarized T-helper cells in a T-helper lymphocyte 2 ( Th2 ) phenotype .

<protein>Interleukin-10</protein> ( <protein>IL-10</protein> ) helps maintain <cell_type>polarized T-helper cells</cell_type> in a <cell_type>T-helper lymphocyte 2 ( Th2 ) phenotype</cell_type> .


Part of this process involves the prevention of the development of Th1 cells , which are a primary source of interferon gamma ( IFNgamma ) , a potent activator of monocytes and an inhibitor of Th2 proliferation .

Part of this process involves the prevention of the development of <cell_type>Th1 cells</cell_type> , which are a primary source of <protein>interferon gamma</protein> ( <protein>IFNgamma</protein> ) , a potent activator of <cell_type>monocytes</cell_type> and an inhibitor of Th2 proliferation .


Because monocytes and macrophages are important mediators of Th1-type responses , such as delayed-type hypersensitivity , we sought to determine if IL-10 could directly mediate inhibition of IFNgamma- and IFNalpha-induced gene expression in these cells .

Because <cell_type>monocytes</cell_type> and macrophages are important mediators of Th1-type responses , such as delayed-type hypersensitivity , we sought to determine if <protein>IL-10</protein> could directly mediate inhibition of IFNgamma- and IFNalpha-induced gene expression in these cells .


Highly purified monocytes were incubated with IL-10 for 60 to 90 minutes before the addition of IFNgamma or IFNalpha .

Highly purified <cell_type>monocytes</cell_type> were incubated with <protein>IL-10</protein> for 60 to 90 minutes before the addition of <protein>IFNgamma</protein> or <protein>IFNalpha</protein> .


IL-10 preincubation resulted in the inhibition of gene expression for several IFN-induced genes , such as IP-10 , ISG54 , and intercellular adhesion molecule-1 .

<protein>IL-10</protein> preincubation resulted in the inhibition of gene expression for several <dna>IFN-induced genes</dna> , such as <protein>IP-10</protein> , <protein>ISG54</protein> , and <protein>intercellular adhesion molecule-1</protein> .


The reduction in gene expression resulted from the ability of IL-10 to suppress IFN -induced assembly of signal transducer and activator of transcription ( STAT ) factors to specific promoter motifs on IFNalpha- and IFNgamma-inducible genes .

The reduction in gene expression resulted from the ability of <protein>IL-10</protein> to suppress <protein>IFN</protein> -induced assembly of <protein>signal transducer and activator of transcription ( STAT ) factors</protein> to <dna>specific promoter motifs</dna> on <dna>IFNalpha- and IFNgamma-inducible genes</dna> .


This was accomplished by preventing the IFN-induced tyrosine phosphorylation of STAT1 , a component of both IFNalpha- and IFNgamma-induced DNA binding complexes .

This was accomplished by preventing the IFN-induced tyrosine phosphorylation of <protein>STAT1</protein> , a component of both <protein>IFNalpha- and IFNgamma-induced DNA binding complexes</protein> .


Therefore , IL-10 can directly inhibit STAT-dependent early response gene expression induced by both IFNalpha and IFNgamma in monocytes by suppressing the tyrosine phosphorylation of STAT1 .

Therefore , <protein>IL-10</protein> can directly inhibit <dna>STAT-dependent early response gene</dna> expression induced by both <protein>IFNalpha</protein> and <protein>IFNgamma</protein> in <cell_type>monocytes</cell_type> by suppressing the tyrosine phosphorylation of <protein>STAT1</protein> .


This may occur through the ability of IL-10 to induce expression of the gene , suppressor of cytokine signaling 3 ( SOCS3 ) .

This may occur through the ability of <protein>IL-10</protein> to induce expression of the gene , suppressor of <protein>cytokine signaling 3</protein> ( <protein>SOCS3</protein> ) .


Clonality analysis of refractory anemia with ring sideroblasts : simultaneous study of clonality and cytochemistry of bone marrow progenitors .

Clonality analysis of refractory anemia with <cell_type>ring sideroblasts</cell_type> : simultaneous study of clonality and cytochemistry of <cell_type>bone marrow progenitors</cell_type> .


X chromosome inactivation and polymorphism of the human androgen receptor ( HUMARA ) gene has been applied for analyzing the clonality of blood cells .

X chromosome inactivation and polymorphism of the <dna>human androgen receptor ( HUMARA ) gene</dna> has been applied for analyzing the clonality of <cell_type>blood cells</cell_type> .


In the present study , the clonal relationship was investigated between peripheral blood polymorphonuclear cells ( PMNCs ) and marrow progenitor cells and the origin of ringed sideroblasts in patients with refractory anemia with ring sideroblasts ( RARS ) by polymerase chain reaction ( PCR ) of HUMARA gene .

In the present study , the clonal relationship was investigated between <cell_type>peripheral blood polymorphonuclear cells</cell_type> ( <cell_type>PMNCs</cell_type> ) and <cell_type>marrow progenitor cells</cell_type> and the origin of <cell_type>ringed sideroblasts</cell_type> in patients with refractory anemia with <cell_type>ring sideroblasts</cell_type> ( <cell_type>RARS</cell_type> ) by polymerase chain reaction ( PCR ) of <dna>HUMARA gene</dna> .


The X-inactivation patterns of circulating PMNCs and T lymphocytes as well as individual granulocyte colonies grown in vitro from bone marrow cells were analyzed .

The X-inactivation patterns of circulating <cell_type>PMNCs</cell_type> and <cell_type>T lymphocytes</cell_type> as well as individual <cell_line>granulocyte colonies</cell_line> grown in vitro from bone marrow cells were analyzed .


The development of ringed sideroblasts in erythroid colonies by iron staining and their X-inactivation pattern were also examined .

The development of <cell_type>ringed sideroblasts</cell_type> in <cell_line>erythroid colonies</cell_line> by iron staining and their X-inactivation pattern were also examined .


All three RARS patients showed monoclonal PMNCs .

All three <cell_type>RARS</cell_type> patients showed monoclonal <cell_type>PMNCs</cell_type> .


In granulocyte colonies , however , two different X-inactivation patterns were observed in all patients , indicating that non-clonal progenitor cells remained in the bone marrow .

In <cell_line>granulocyte colonies</cell_line> , however , two different X-inactivation patterns were observed in all patients , indicating that <cell_type>non-clonal progenitor cells</cell_type> remained in the bone marrow .


All erythroid colonies consisted of ringed sideroblasts exclusively showed one pattern dominant in those of PMNCs .

All <cell_line>erythroid colonies</cell_line> consisted of <cell_type>ringed sideroblasts</cell_type> exclusively showed one pattern dominant in those of <cell_type>PMNCs</cell_type> .


Our findings suggest that non-clonal progenitor cells persist in some RARS cases , that erythroid progenitors show mosaicism , and that ringed sideroblasts may be derived from an abnormal clone involved in the pathogenesis of this disease .

Our findings suggest that <cell_type>non-clonal progenitor cells</cell_type> persist in some <cell_type>RARS</cell_type> cases , that <cell_type>erythroid progenitors</cell_type> show mosaicism , and that <cell_type>ringed sideroblasts</cell_type> may be derived from an abnormal clone involved in the pathogenesis of this disease .


Granulosa cell tumor of the ovary .


Immunohistochemical evidence of low proliferative activity and virtual absence of mutation of the p53 tumor-suppressor gene .

Immunohistochemical evidence of low proliferative activity and virtual absence of mutation of the <dna>p53 tumor-suppressor gene</dna> .


BACKGROUND AND METHODS : Because the use of immunohistochemistry in the diagnosis of granulosa cell tumor ( GCT ) has not been fully explored , routinely processed ( formalin-fixed , paraffin-embedded ) tissue from 11 GCT , adult type , was investigated immunohistochemically ( ABC method ) with a broad spectrum of antibodies against various markers , including p53 and Ki-67 .

BACKGROUND AND METHODS : Because the use of immunohistochemistry in the diagnosis of granulosa cell tumor ( GCT ) has not been fully explored , routinely processed ( formalin-fixed , paraffin-embedded ) tissue from 11 GCT , adult type , was investigated immunohistochemically ( ABC method ) with a broad spectrum of antibodies against various markers , including <protein>p53</protein> and <protein>Ki-67</protein> .


All of the tumors exhibited typical morphology , were limited to the ovary ( stage I ) , and 7 cases followed a benign clinical course .


RESULTS : All the tumors exhibited strong expression of vimentin , but most other antigens ( including smooth muscle actin ) were expressed infrequently by a minority of tumor cells or not at all .

RESULTS : All the tumors exhibited strong expression of <protein>vimentin</protein> , but most other antigens ( including <protein>smooth muscle actin</protein> ) were expressed infrequently by a minority of <cell_type>tumor cells</cell_type> or not at all .


Tumor cells in 9 GCT expressed inhibin A .


All the tumors exhibited very low proliferative activity , fewer than 10 % of the tumor cell nuclei being stained by the antibody MIB-1 ( Ki-67 antigen ) .

All the tumors exhibited very low proliferative activity , fewer than 10 % of the tumor cell nuclei being stained by the <protein>antibody MIB-1</protein> ( <protein>Ki-67 antigen</protein> ) .


The antibody D07 revealed marked overexpression of p53 protein in only one tumor .

The <protein>antibody D07</protein> revealed marked overexpression of <protein>p53 protein</protein> in only one tumor .


Clinical outcome was not found to be related to immunophenotypic differences .


CONCLUSIONS : The diagnosis of GCT should be based primarily on the typical morphology revealed by conventional stains , but additional immunohistochemical staining with a small panel of selected antibodies ( for example , against keratin , vimentin , and inhibin A ) may be helpful in a few cases .

CONCLUSIONS : The diagnosis of GCT should be based primarily on the typical morphology revealed by conventional stains , but additional immunohistochemical staining with a small panel of selected antibodies ( for example , against <protein>keratin</protein> , <protein>vimentin</protein> , and <protein>inhibin A</protein> ) may be helpful in a few cases .


The very low proliferative activity and the lack of overexpression of p53 protein are consistent with the benign clinical behavior of the majority of GCT .

The very low proliferative activity and the lack of overexpression of <protein>p53 protein</protein> are consistent with the benign clinical behavior of the majority of GCT .


Protective effects of notch-1 on TCR -induced apoptosis .

Protective effects of <protein>notch-1</protein> on <protein>TCR</protein> -induced apoptosis .


The Notch receptor protein was originally identified in Drosophila and is known to mediate cell to cell communication and influence cell fate decisions .

The <protein>Notch receptor protein</protein> was originally identified in Drosophila and is known to mediate cell to cell communication and influence cell fate decisions .


Members of this family have been isolated from invertebrates as well as vertebrates .


We isolated mouse Notch-1 in a yeast two-hybrid screen with Nur77 , which is a protein that has been shown previously to be required for apoptosis in T cell lines .

We isolated <protein>mouse Notch-1</protein> in a yeast two-hybrid screen with <protein>Nur77</protein> , which is a protein that has been shown previously to be required for apoptosis in <cell_line>T cell lines</cell_line> .


The data presented below indicate that Notch-1 expression provides significant protection to T cell lines from TCR -mediated apoptosis .

The data presented below indicate that <protein>Notch-1</protein> expression provides significant protection to <cell_line>T cell lines</cell_line> from <protein>TCR</protein> -mediated apoptosis .


These data demonstrate a new antiapoptotic role for Notch-1 , providing evidence that , in addition to regulating cell fate decisions , Notch-1 can play a critical role in controlling levels of cell death in T cells .

These data demonstrate a new antiapoptotic role for <protein>Notch-1</protein> , providing evidence that , in addition to regulating cell fate decisions , <protein>Notch-1</protein> can play a critical role in controlling levels of cell death in <cell_type>T cells</cell_type> .


Comparison of primary sensitization of naive human T cells to varicella-zoster virus peptides by dendritic cells in vitro with responses elicited in vivo by varicella vaccination .

Comparison of primary sensitization of <cell_type>naive human T cells</cell_type> to varicella-zoster virus peptides by <cell_type>dendritic cells</cell_type> in vitro with responses elicited in vivo by varicella vaccination .


Dendritic cells ( DC ) are potent APC during primary and secondary immune responses .

<cell_type>Dendritic cells</cell_type> ( <cell_type>DC</cell_type> ) are potent <cell_type>APC</cell_type> during primary and secondary immune responses .


The first objective of this study was to determine whether human DC mediate in vitro sensitization of naive CD4+ T cells to epitopes of the immediate early 62 ( IE62 ) protein of varicella zoster virus ( VZV ) .

The first objective of this study was to determine whether <cell_type>human DC</cell_type> mediate in vitro sensitization of <cell_type>naive CD4+ T cells</cell_type> to <protein>epitopes</protein> of the <protein>immediate early 62 ( IE62 ) protein</protein> of varicella zoster virus ( VZV ) .


The induction of CD4+ T cell proliferative responses to eight synthetic peptides representing amino acid sequences of the VZV IE62 protein was assessed using T cells and DC from VZV-susceptible donors .

The induction of <protein>CD4+</protein> T cell proliferative responses to eight synthetic peptides representing amino acid sequences of the <protein>VZV IE62 protein</protein> was assessed using <cell_type>T cells</cell_type> and <cell_type>DC</cell_type> from VZV-susceptible donors .


The second objective was to compare in vitro responses of naive T cells with responses to VZV peptides induced in vivo after immunization with varicella vaccine .

The second objective was to compare in vitro responses of <cell_type>naive T cells</cell_type> with responses to VZV peptides induced in vivo after immunization with varicella vaccine .


T cell proliferation was induced by three peptides , P1 , P4 , and P7 , in 71-100 % of the donors tested before and after vaccination using DC as APC .

T cell proliferation was induced by three peptides , P1 , P4 , and P7 , in 71-100 % of the donors tested before and after vaccination using <cell_type>DC</cell_type> as <cell_type>APC</cell_type> .


Monocytes were effective APC for VZV peptides only after immunization .

<cell_type>Monocytes</cell_type> were effective <cell_type>APC</cell_type> for VZV peptides only after immunization .


Two peptides , P2 and P8 , induced naive T cell proliferation less effectively and were also less immunogenic for T cells from vaccinated or naturally immune donors .

Two peptides , P2 and P8 , induced naive T cell proliferation less effectively and were also less immunogenic for <cell_type>T cells</cell_type> from vaccinated or naturally immune donors .


T cell recognition of specific peptides was concordant between naive , DC -mediated responses , and postvaccine responses using monocytes as APC in 69 % of comparisons ( p = 0.05 ; chi2 ) ; the predictive value of a positive response to an IE62 peptide before immunization for T cell sensitization in vivo was 82 % .

T cell recognition of specific peptides was concordant between naive , <cell_type>DC</cell_type> -mediated responses , and postvaccine responses using <cell_type>monocytes</cell_type> as <cell_type>APC</cell_type> in 69 % of comparisons ( p = 0.05 ; chi2 ) ; the predictive value of a positive response to an IE62 peptide before immunization for T cell sensitization in vivo was 82 % .


These observations indicate that primary T cell responses detected in vitro using DC as APC may be useful to characterize the potential immunogenicity of viral protein epitopes in vivo .

These observations indicate that primary T cell responses detected in vitro using <cell_type>DC</cell_type> as <cell_type>APC</cell_type> may be useful to characterize the potential immunogenicity of viral protein epitopes in vivo .


Mechanism of interleukin-10 inhibition of T-helper cell activation by superantigen at the level of the cell cycle .

Mechanism of <protein>interleukin-10</protein> inhibition of T-helper cell activation by <protein>superantigen</protein> at the level of the cell cycle .


We have analyzed the effects of interleukin-10 ( IL-10 ) on the entry of quiescent CD4 ( + ) T cells into the cell cycle upon stimulation with the superantigen staphylococcal enterotoxin B ( SEB ) .

We have analyzed the effects of <protein>interleukin-10</protein> ( <protein>IL-10</protein> ) on the entry of quiescent <cell_type>CD4 ( + ) T cells</cell_type> into the cell cycle upon stimulation with the <protein>superantigen</protein> <protein>staphylococcal enterotoxin B</protein> ( <protein>SEB</protein> ) .


IL-10 arrested cells at G0/G1 .

<protein>IL-10</protein> arrested cells at G0/G1 .


IL-10 treatment prevented the downregulation of p27 ( Kip1 ) , an inhibitory protein that controls progression out of the G0 phase of the cell cycle .

<protein>IL-10</protein> treatment prevented the downregulation of <protein>p27 ( Kip1</protein> ) , an <protein>inhibitory protein</protein> that controls progression out of the G0 phase of the cell cycle .


IL-10 also prevented the upregulation of the G1 cyclins D2 and D3 , proteins necessary for entry and progression through the G1 phase of the cell cycle .

<protein>IL-10</protein> also prevented the upregulation of the <protein>G1 cyclins</protein> <protein>D2</protein> and <protein>D3</protein> , proteins necessary for entry and progression through the G1 phase of the cell cycle .


Associated with the inhibition of the cell cycle , IL-10 suppressed SEB induction of interleukin-2 ( IL-2 ) .

Associated with the inhibition of the cell cycle , <protein>IL-10</protein> suppressed <protein>SEB</protein> induction of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) .


Addition of exogenous IL-2 to IL-10-treated cells significantly reversed the antiproliferative effects of IL-10 .

Addition of exogenous <protein>IL-2</protein> to <cell_line>IL-10-treated cells</cell_line> significantly reversed the antiproliferative effects of <protein>IL-10</protein> .


Moreover , IL-10 effects on the early G1 proteins p27 ( Kip1 ) and cyclin D2 were similarly reversed by exogenous IL-2 .

Moreover , <protein>IL-10</protein> effects on the <protein>early G1 proteins</protein> <protein>p27 ( Kip1 )</protein> and <protein>cyclin D2</protein> were similarly reversed by exogenous <protein>IL-2</protein> .


Although this reversal by IL-2 was pronounced , it was not complete , suggesting that IL-10 may have some effects not directly related to the suppression of IL-2 production .

Although this reversal by <protein>IL-2</protein> was pronounced , it was not complete , suggesting that <protein>IL-10</protein> may have some effects not directly related to the suppression of <protein>IL-2</protein> production .


Cell separation experiments suggest that IL-10 can effect purified CD4 ( + ) T cells directly , providing functional evidence for the presence of IL-10 receptors on CD4 ( + ) T cells .

Cell separation experiments suggest that <protein>IL-10</protein> can effect purified <cell_type>CD4 ( + ) T cells</cell_type> directly , providing functional evidence for the presence of <protein>IL-10</protein> receptors on <cell_type>CD4 ( + ) T cells</cell_type> .


IL-10 also inhibited expression of IL-2 transcriptional regulators c-fos and c-jun , which also inhibit other cell functions .

<protein>IL-10</protein> also inhibited expression of <protein>IL-2 transcriptional regulators</protein> <protein>c-fos</protein> and <protein>c-jun</protein> , which also inhibit other cell functions .


Our studies show that the mechanism of IL-10 regulation of quiescent CD4 ( + ) T-cell activation is mainly by blocking induction of IL-2 that is critical to downregulation of p27 ( Kip1 ) and upregulation of D cyclins in T-cell activation and entry into the cell cycle .

Our studies show that the mechanism of <protein>IL-10</protein> regulation of quiescent CD4 ( + ) T-cell activation is mainly by blocking induction of <protein>IL-2</protein> that is critical to downregulation of <protein>p27 ( Kip1 )</protein> and upregulation of <protein>D cyclins</protein> in T-cell activation and entry into the cell cycle .


IFN-gamma and IL-10 inhibit induction of IL-1 receptor type I and type II gene expression by IL-4 and IL-13 in human monocytes .

<protein>IFN-gamma</protein> and <protein>IL-10</protein> inhibit induction of IL-1 receptor type I and type II gene expression by <protein>IL-4</protein> and <protein>IL-13</protein> in human <cell_type>monocytes</cell_type> .


The Th2-type cytokines IL-4 and IL-13 induce expression of a distinct subset of genes in human monocytes .

The <protein>Th2-type cytokines</protein> <protein>IL-4</protein> and <protein>IL-13</protein> induce expression of a distinct subset of genes in <cell_type>human monocytes</cell_type> .


These include Fc epsilonRII ( CD23 ) , 15-lipoxygenase , IL-1 receptor antagonist ( IL-1ra ) , and type I and type II IL-1 receptors ( IL-1R ) .

These include <protein>Fc epsilonRII</protein> ( <protein>CD23</protein> ) , <protein>15-lipoxygenase</protein> , <protein>IL-1 receptor antagonist</protein> ( <protein>IL-1ra</protein> ) , and <protein>type I and type II IL-1 receptors</protein> ( <protein>IL-1R</protein> ) .


IFN-gamma has been shown to inhibit induction of CD23 and 15-lipoxygenase in monocytes ; however , the effects of IFN-gamma on type I and type II IL-1R gene expression have not been defined .

<protein>IFN-gamma</protein> has been shown to inhibit induction of <protein>CD23</protein> and <protein>15-lipoxygenase</protein> in <cell_type>monocytes</cell_type> ; however , the effects of <protein>IFN-gamma</protein> on type I and type II IL-1R gene expression have not been defined .


We examined the effects of IFN-gamma on both basal and IL-4 / IL-13 -induced IL-1R gene expression in primary monocytes .

We examined the effects of <protein>IFN-gamma</protein> on both basal and <protein>IL-4</protein> / <protein>IL-13</protein> -induced <dna>IL-1R gene</dna> expression in <cell_type>primary monocytes</cell_type> .


IL-4 and IL-13 induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA levels .

<protein>IL-4</protein> and <protein>IL-13</protein> induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA levels .


IFN-gamma decreased basal expression as well as the induction of these genes by IL-4 and IL-13 .

<protein>IFN-gamma</protein> decreased basal expression as well as the induction of these genes by <protein>IL-4</protein> and <protein>IL-13</protein> .


Inhibition of IL-1RI and IL-1RII mRNA levels by IFN-gamma was transcriptionally mediated , and correlated directly with decreased production of soluble IL-1RII .

Inhibition of <protein>IL-1RI</protein> and IL-1RII mRNA levels by <protein>IFN-gamma</protein> was transcriptionally mediated , and correlated directly with decreased production of soluble <protein>IL-1RII</protein> .


Furthermore , the ability to suppress IL-1RI and IL-1RII mRNA levels was not unique to IFN-gamma because IL-10 also inhibited expression of these genes in IL-4/IL-13-stimulated monocytes .

Furthermore , the ability to suppress IL-1RI and <protein>IL-1RII</protein> mRNA levels was not unique to <protein>IFN-gamma</protein> because <protein>IL-10</protein> also inhibited expression of these genes in <cell_line>IL-4/IL-13-stimulated monocytes</cell_line> .


Inhibition of IL-1R gene expression by IFN-gamma and IL-10 was not due to down-regulation of surface IL-4R because pretreatment with these cytokines did not decrease the number of IL-4 binding sites per cell .

Inhibition of <dna>IL-1R gene</dna> expression by <protein>IFN-gamma</protein> and <protein>IL-10</protein> was not due to down-regulation of <protein>surface IL-4R</protein> because pretreatment with these cytokines did not decrease the number of <protein>IL-4</protein> binding sites per cell .


However , suppression of IL-1R gene expression by IFN-gamma and IL-10 was associated with decreased tyrosine phosphorylation and nuclear translocation of the IL-4/IL-13-inducible transcription factor , Stat6 , suggesting a potential mechanism by which IFN-gamma and IL-10 may mediate their suppressive effects .

However , suppression of <dna>IL-1R gene</dna> expression by <protein>IFN-gamma</protein> and <protein>IL-10</protein> was associated with decreased tyrosine phosphorylation and nuclear translocation of the <protein>IL-4/IL-13-inducible transcription factor</protein> , <protein>Stat6</protein> , suggesting a potential mechanism by which <protein>IFN-gamma</protein> and <protein>IL-10</protein> may mediate their suppressive effects .


These findings demonstrate that certain cytokines , including IFN-gamma and IL-10 , antagonize the ability of IL-4 and IL-13 to induce increased expression of the IL-1RI and IL-1RII genes in monocytes .

These findings demonstrate that certain cytokines , including <protein>IFN-gamma</protein> and <protein>IL-10</protein> , antagonize the ability of <protein>IL-4</protein> and <protein>IL-13</protein> to induce increased expression of the IL-1RI and <dna>IL-1RII genes</dna> in <cell_type>monocytes</cell_type> .


Cytokine rescue from glucocorticoid induced apoptosis in T cells is mediated through inhibition of IkappaBalpha .

<protein>Cytokine</protein> rescue from glucocorticoid induced apoptosis in <cell_type>T cells</cell_type> is mediated through inhibition of <protein>IkappaBalpha</protein> .


We previously reported that dexamethasone ( DEX ) , a synthetic glucocorticoid , causes apoptosis in mature Th cell lines , and that this induction of cell death is prevented by specific cytokines , namely , by IL-2 in Th1 cells and by IL-4 in Th2 cells .

We previously reported that dexamethasone ( DEX ) , a synthetic glucocorticoid , causes apoptosis in <cell_line>mature Th cell lines</cell_line> , and that this induction of cell death is prevented by specific <protein>cytokines</protein> , namely , by <protein>IL-2</protein> in <cell_type>Th1 cells</cell_type> and by <protein>IL-4</protein> in <cell_type>Th2 cells</cell_type> .


We now show that this differential rescue by specific cytokines in Th cells correlates with the level of IkappaBalpha that is regulated by DEX and cytokines .

We now show that this differential rescue by specific <protein>cytokines</protein> in <cell_type>Th cells</cell_type> correlates with the level of <protein>IkappaBalpha</protein> that is regulated by DEX and <protein>cytokines</protein> .


In both cell types the cellular levels of IkappaBalpha mRNA and protein were evaluated by DEX treatment .

In both cell types the cellular levels of <rna>IkappaBalpha mRNA</rna> and protein were evaluated by DEX treatment .


Interestingly , the DEX-mediated IkappaBalpha induction was completely inhibited by IL-2 , but not IL-4 , in Th1 cells , while the reverse profile was seen in Th2 cells .

Interestingly , the DEX-mediated <protein>IkappaBalpha</protein> induction was completely inhibited by <protein>IL-2</protein> , but not <protein>IL-4</protein> , in <cell_type>Th1 cells</cell_type> , while the reverse profile was seen in <cell_type>Th2 cells</cell_type> .


In both cell types , the cytokine that inhibits the induction of IkappaBalpha by DEX , also rescues these cells from DEX-induced apoptosis , although the rescue cytokine is different in Th1 and Th2 cells .

In both cell types , the <protein>cytokine</protein> that inhibits the induction of <protein>IkappaBalpha</protein> by DEX , also rescues these cells from DEX-induced apoptosis , although the rescue cytokine is different in <cell_type>Th1 and Th2 cells</cell_type> .


Our results imply that T cells need to maintain a certain level of NF-kappaB transcriptional activity in order to survive ; up- or down-regulation of nuclear NF kappaB through modulation of IkappaBalpha expression by cytokines or DEX may lead to cell survival or cell death , respectively .

Our results imply that <cell_type>T cells</cell_type> need to maintain a certain level of <protein>NF-kappaB</protein> transcriptional activity in order to survive ; up- or down-regulation of <protein>nuclear NF kappaB</protein> through modulation of <protein>IkappaBalpha</protein> expression by <protein>cytokines</protein> or DEX may lead to cell survival or cell death , respectively .


Expression of transcription factor genes after influenza A virus infection .

Expression of <dna>transcription factor genes</dna> after influenza A virus infection .


Infection of human monocytes with influenza A virus induces a broad range of proinflammatory cytokines and mononuclear cell attracting chemokines before the infected cells undergo apoptosis .

Infection of human <cell_type>monocytes</cell_type> with influenza A virus induces a broad range of <protein>proinflammatory cytokines</protein> and mononuclear cell attracting <protein>chemokines</protein> before the <cell_type>infected cells</cell_type> undergo apoptosis .


The underlying mechanisms by which the corresponding genes are transcriptionally initiated after virus infection are still poorly understood .


Activation of NF-kappa B seems to play an important role in the regulation of many proinflammatory cytokine genes , but can not be the only mechanism , since several cytokine genes lack respective binding sites in their promoter regions .

Activation of <protein>NF-kappa B</protein> seems to play an important role in the regulation of many <dna>proinflammatory cytokine genes</dna> , but can not be the only mechanism , since several <dna>cytokine genes</dna> lack respective <dna>binding sites</dna> in their <dna>promoter regions</dna> .


Therefore , we additionally investigated other transcription factors of possible importance such as CREB , CTF , OTF-1 , and OTF-2 .

Therefore , we additionally investigated other <protein>transcription factors</protein> of possible importance such as <protein>CREB</protein> , <protein>CTF</protein> , <protein>OTF-1</protein> , and <protein>OTF-2</protein> .


To explore long-term regulatory mechanisms , we investigated the induction of transcription factors on the gene expression level which may be important to substitute for metabolized transcription factor proteins after their activation .

To explore long-term regulatory mechanisms , we investigated the induction of <protein>transcription factors</protein> on the gene expression level which may be important to substitute for <protein>metabolized transcription factor proteins</protein> after their activation .


We identified a cell-type-specific differential response : CREB , CTF , OTF-1 , OFT-2 , and NF-kappa B genes were strongly induced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6 , while in freshly prepared human monocytes no significant changes were detected .

We identified a cell-type-specific differential response : <dna>CREB , CTF , OTF-1 , OFT-2 , and NF-kappa B genes</dna> were strongly induced 1 to 4 hours after influenza A virus infection in the <cell_line>monocytic cell line</cell_line> <cell_line>Mono Mac 6</cell_line> , while in freshly prepared human <cell_type>monocytes</cell_type> no significant changes were detected .


In infected monocytes , which die by apoptosis , the expression of CREB , CTF , and OTF-2 was rather suppressed 8 hours after infection .

In infected <cell_type>monocytes</cell_type> , which die by apoptosis , the expression of <protein>CREB</protein> , <protein>CTF</protein> , and <protein>OTF-2</protein> was rather suppressed 8 hours after infection .


In conclusion , the long-term regulation of transcription factor gene expression in non-proliferating cells seems to be of minor importance after influenza infection since in apoptosisprone cells an immediate availability of transcription factor proteins is required .

In conclusion , the long-term regulation of <protein>transcription factor</protein> gene expression in <cell_type>non-proliferating cells</cell_type> seems to be of minor importance after influenza infection since in <cell_type>apoptosisprone cells</cell_type> an immediate availability of <protein>transcription factor proteins</protein> is required .


Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB .

<cell_type>Peripheral blood mononuclear cells</cell_type> isolated from patients with diabetic nephropathy show increased activation of the <protein>oxidative-stress sensitive transcription factor</protein> <protein>NF-kappaB</protein> .


Increased oxidative stress and subsequent activation of the transcription factor NF-kappaB has been linked to the development of late diabetic complications .

Increased oxidative stress and subsequent activation of the transcription factor <protein>NF-kappaB</protein> has been linked to the development of late diabetic complications .


To determine whether oxidative stress dependent NF-kappaB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kappaB activation in ex vivo isolated peripheral blood mononuclear cells .

To determine whether oxidative stress dependent <protein>NF-kappaB</protein> activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine <protein>NF-kappaB</protein> activation in ex vivo <cell_type>isolated peripheral blood mononuclear cells</cell_type> .


We examined 33 patients with diabetes mellitus ( Type I and Type II ) .


Patients with diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications .

Patients with diabetic nephropathy showed higher <protein>NF-kappaB</protein> binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated <protein>NF-kappaBp65</protein> than patients without renal complications .


NF-kappaB binding activity correlated with the degree of albuminuria ( r = 0.316 ) and with thrombomodulin plasma concentrations ( r = 0.33 ) , indicative for albuminuria associated endothelial dysfunction .

<protein>NF-kappaB</protein> binding activity correlated with the degree of albuminuria ( r = 0.316 ) and with <protein>thrombomodulin</protein> plasma concentrations ( r = 0.33 ) , indicative for albuminuria associated endothelial dysfunction .


In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid ( alpha-lipoic acid ) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48 % and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38 % .

In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid ( alpha-lipoic acid ) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48 % and <protein>NF-kappaB</protein> binding activity in ex vivo <cell_type>isolated peripheral blood mononuclear cells</cell_type> by 38 % .


In conclusion , activation of the transcription factor NF-kappaB in ex vivo isolated peripheral blood mononuclear cells of patients with diabetes mellitus correlates with the degree of diabetic nephropathy .

In conclusion , activation of the <protein>transcription factor</protein> <protein>NF-kappaB</protein> in ex vivo <cell_type>isolated peripheral blood mononuclear cells</cell_type> of patients with diabetes mellitus correlates with the degree of diabetic nephropathy .


NF-kappaB activation is at least in part dependent on oxidative stress since thioctic acid ( alpha-lipoic acid ) reduced NF-kappaB binding activity .

<protein>NF-kappaB</protein> activation is at least in part dependent on oxidative stress since thioctic acid ( alpha-lipoic acid ) reduced <protein>NF-kappaB</protein> binding activity .


Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors .

<protein>Osteoclast markers</protein> accumulate on cells developing from <cell_type>human peripheral blood mononuclear precursors</cell_type> .


Recent studies show that human osteoclasts develop in vitro from hematopoietic cells ; however , special cultures conditions and/or cytokine mobilized peripheral blood are apparently required .

Recent studies show that <cell_type>human osteoclasts</cell_type> develop in vitro from <cell_type>hematopoietic cells</cell_type> ; however , special cultures conditions and/or cytokine mobilized peripheral blood are apparently required .


Here , we report that cells expressing osteoclast markers differentiate from precursors present in nonmobilized peripheral blood mononuclear cells ( PBMC ) , without the addition of stromal cells , growth factors , cytokines or steroids ; and characterize their phenotype .

Here , we report that cells expressing <protein>osteoclast markers</protein> differentiate from precursors present in <cell_type>nonmobilized peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) , without the addition of <cell_type>stromal cells</cell_type> , <protein>growth factors</protein> , cytokines or steroids ; and characterize their phenotype .


Three days after establishing high-density PBMC cultures ( 1.5 x 10 ( 6 ) cells/cm2 ) , in serum-containing medium , small adherent colonies of tartrate resistant acid phosphatase positive ( TRAP+ ) cells emerge , amidst massive monocyte cell death .

Three days after establishing high-density <cell_type>PBMC</cell_type> cultures ( 1.5 x 10 ( 6 ) cells/cm2 ) , in serum-containing medium , small <cell_line>adherent colonies</cell_line> of <cell_line>tartrate resistant acid phosphatase positive ( TRAP+ ) cells</cell_line> emerge , amidst massive monocyte cell death .


These adherent cells have an eccentrically placed , round nucleus , and express low levels of TRAP and sodium fluoride-resistant- alpha-naphthyl-acetate-esterase ( NaF-R-NSE ) .

These <cell_type>adherent cells</cell_type> have an eccentrically placed , round nucleus , and express low levels of <protein>TRAP</protein> and <protein>sodium fluoride-resistant- alpha-naphthyl-acetate-esterase</protein> ( <protein>NaF-R-NSE</protein> ) .


Over the next week , this cell population accumulates phenotypic markers of osteoclasts ( vitronectin receptor [ VR ] , calcitonin receptor , TRAP , cathepsin K protein , and mRNA ) with increased nuclearity , covering the entire surface by 15 days .

Over the next week , this cell population accumulates phenotypic markers of <cell_type>osteoclasts</cell_type> ( <protein>vitronectin receptor</protein> [ <protein>VR</protein> ] , <protein>calcitonin receptor</protein> , <protein>TRAP</protein> , <protein>cathepsin K protein</protein> , and <rna>mRNA</rna> ) with increased nuclearity , covering the entire surface by 15 days .


When cultured on bone , VR+ , TRAP+ cells of low multinuclearity appear and cover up to 50 % of the surface .

When cultured on bone , <cell_line>VR+ , TRAP+ cells</cell_line> of low multinuclearity appear and cover up to 50 % of the surface .


Resorption lacunae can be observed by day 22 .


Although these pits are not nearly as numerous as the cells of preosteoclast phenotype , they do represent the activity of a subset of osteoclast-like cells that has achieved osteoclastic maturity under these culture conditions .

Although these pits are not nearly as numerous as the cells of <cell_type>preosteoclast phenotype</cell_type> , they do represent the activity of a subset of <cell_type>osteoclast-like cells</cell_type> that has achieved osteoclastic maturity under these culture conditions .


Transcripts for osteoprotegerin ligand ( OPGL ) , an osteoclast differentiation factor ( also known as RANKL and TRANCE ) are expressed , likely by adherent cells .

Transcripts for <protein>osteoprotegerin ligand</protein> ( <protein>OPGL</protein> ) , an <protein>osteoclast differentiation factor</protein> ( also known as <protein>RANKL</protein> and <protein>TRANCE</protein> ) are expressed , likely by <cell_type>adherent cells</cell_type> .


Thus , an adherent population of cells , with preosteoclast/ osteoclast phenotypic properties , arises selectively under simple culture conditions from normal PBMC .

Thus , an adherent population of cells , with preosteoclast/ <cell_type>osteoclast</cell_type> phenotypic properties , arises selectively under simple culture conditions from normal <cell_type>PBMC</cell_type> .


Further characterization of these cells should identify factors involved in the growth , terminal differentiation and activation of osteoclasts .

Further characterization of these cells should identify factors involved in the growth , terminal differentiation and activation of <cell_type>osteoclasts</cell_type> .


Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet .


Because oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet , we investigated whether this fatty acid can modulate endothelial activation , ie , the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis .

Because oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet , we investigated whether this fatty acid can modulate endothelial activation , ie , the concerted expression of <protein>gene products</protein> involved in leukocyte recruitment and early atherogenesis .


We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours , followed by coincubation of oleate with human recombinant tumor necrosis factor , interleukin ( IL ) -1alpha , IL-1beta , IL-4 , Escherichia coli lipopolysaccharide ( LPS ) , or phorbol 12-myristate 13-acetate for a further 6 to 24 hours .

We incubated sodium oleate with <cell_type>human umbilical vein endothelial cells</cell_type> for 0 to 72 hours , followed by coincubation of oleate with <protein>human recombinant tumor necrosis factor</protein> , <protein>interleukin ( IL ) -1alpha</protein> , <protein>IL-1beta</protein> , <protein>IL-4</protein> , Escherichia coli lipopolysaccharide ( LPS ) , or phorbol 12-myristate 13-acetate for a further 6 to 24 hours .


The endothelial expression of vascular cell adhesion molecule-1 ( VCAM-1 ) , E-selectin , and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry , and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis .

The endothelial expression of <protein>vascular cell adhesion molecule-1</protein> ( <protein>VCAM-1</protein> ) , <protein>E-selectin</protein> , and <protein>intercellular adhesion molecule-1</protein> was monitored by cell surface enzyme immunoassays or flow cytometry , and steady-state levels of <rna>VCAM-1 mRNA</rna> were assessed by Northern blot analysis .


At 10 to 100 micromol/L for > 24 hours , oleate inhibited the expression of all adhesion molecules tested .

At 10 to 100 micromol/L for > 24 hours , oleate inhibited the expression of all <protein>adhesion molecules</protein> tested .


After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS , VCAM-1 expression was reduced by > 40 % compared with control .

After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS , <protein>VCAM-1</protein> expression was reduced by > 40 % compared with control .


Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly .

Adhesion of <cell_line>monocytoid U937 cells</cell_line> to LPS-treated endothelial cells was reduced concomitantly .


Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays .

Oleate also produced a quantitatively similar reduction of <rna>VCAM-1 mRNA</rna> levels on Northern blot analysis and inhibited <protein>nuclear factor-kappaB</protein> activation on electrophoretic mobility shift assays .


Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated ( palmitic and stearic ) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids .

Incubation of <cell_type>endothelial cells</cell_type> with oleate for 72 hours decreased the relative proportions of saturated ( palmitic and stearic ) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids .


Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation , oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment .


Both Stat3 -activation and Stat3 -independent BCL2 downregulation are important for interleukin-6 -induced apoptosis of 1A9-M cells .

Both <protein>Stat3</protein> -activation and <protein>Stat3</protein> -independent <protein>BCL2</protein> downregulation are important for <protein>interleukin-6</protein> -induced apoptosis of <cell_line>1A9-M cells</cell_line> .


A unique subclone of a bone marrow-derived stromal cell line , BMS2.4 , produces soluble factors that inhibit proliferation of several types of hematopoietic cell lines .

A unique subclone of a <cell_line>bone marrow-derived stromal cell line</cell_line> , <cell_line>BMS2.4</cell_line> , produces <protein>soluble factors</protein> that inhibit proliferation of several types of <cell_line>hematopoietic cell lines</cell_line> .


An understanding of these molecules may be informative about negative regulatory circuits that can potentially limit blood cell formation .


We used expression cloning to identify interleukin-6 ( IL-6 ) as one factor that suppressed growth of a pre-B-cell variant line , 1A9-M .

We used expression cloning to identify <protein>interleukin-6</protein> ( <protein>IL-6</protein> ) as one factor that suppressed growth of a <cell_line>pre-B-cell variant line</cell_line> , <cell_line>1A9-M</cell_line> .


Moreover , IL-6 induced macrophage-differentiation and apoptosis of 1A9-M cells .

Moreover , <protein>IL-6</protein> induced macrophage-differentiation and apoptosis of <cell_line>1A9-M cells</cell_line> .


During this process , IL-6 downregulated expression of BCL2 in 1A9-M cells and stimulated BCL-XL expression , but had no effect on p53 , Bax , or Bak gene expression .

During this process , <protein>IL-6</protein> downregulated expression of <protein>BCL2</protein> in <cell_line>1A9-M cells</cell_line> and stimulated BCL-XL expression , but had no effect on p53 , Bax , or Bak gene expression .


Mechanisms for transduction of IL-6 -induced signals were then evaluated in IL-6-stimulated 1A9-M cells .

Mechanisms for transduction of <protein>IL-6</protein> -induced signals were then evaluated in <cell_line>IL-6-stimulated 1A9-M cells</cell_line> .


Whereas the signal transducer and activator of transcription 3 ( Stat3 ) was phosphorylated and activated , there was no effect on either Stat1 or Stat5 .

Whereas the <protein>signal transducer and activator of transcription 3</protein> ( <protein>Stat3</protein> ) was phosphorylated and activated , there was no effect on either <protein>Stat1</protein> or <protein>Stat5</protein> .


The importance of BCL2 and Stat3 on IL-6 -induced macrophage-differentiation and apoptosis was studied with 1A9-M cells expressing human BCL2 or a dominant-negative form of Stat3 , respectively .

The importance of <protein>BCL2</protein> and <protein>Stat3</protein> on <protein>IL-6</protein> -induced macrophage-differentiation and apoptosis was studied with <cell_line>1A9-M cells</cell_line> expressing <protein>human BCL2</protein> or a dominant-negative form of <protein>Stat3</protein> , respectively .


IL-6 -induced apoptosis , but not macrophage-differentiation , was blocked by continuously expressed BCL2 .

<protein>IL-6</protein> -induced apoptosis , but not macrophage-differentiation , was blocked by continuously expressed <protein>BCL2</protein> .


A dominant-negative form of Stat3 inhibited both macrophage-differentiation and apoptosis induced by IL-6 .

A <protein>dominant-negative form of Stat3</protein> inhibited both macrophage-differentiation and apoptosis induced by <protein>IL-6</protein> .


However , diminished Stat3 activity did not prevent IL-6 -induced downregulation of the BCL2 gene .

However , diminished <protein>Stat3</protein> activity did not prevent <protein>IL-6</protein> -induced downregulation of the <dna>BCL2 gene</dna> .


Therefore , activation of Stat3 is essential for IL-6 -induced macrophage-differentiation and programmed cell death in this model .

Therefore , activation of <protein>Stat3</protein> is essential for <protein>IL-6</protein> -induced macrophage-differentiation and programmed cell death in this model .


Whereas overexpression of BCL2 abrogates the apoptotic response , Stat3 -independent signals appear to downregulate expression of the BCL2 gene .

Whereas overexpression of <protein>BCL2</protein> abrogates the apoptotic response , <protein>Stat3</protein> -independent signals appear to downregulate expression of the <dna>BCL2 gene</dna> .


Involvement of mitogen-activated protein kinase pathways in interleukin-8 production by human monocytes and polymorphonuclear cells stimulated with lipopolysaccharide or Mycoplasma fermentans membrane lipoproteins .

Involvement of <protein>mitogen-activated protein kinase</protein> pathways in <protein>interleukin-8</protein> production by <cell_type>human monocytes</cell_type> and <cell_type>polymorphonuclear cells</cell_type> stimulated with lipopolysaccharide or <protein>Mycoplasma fermentans membrane lipoproteins</protein> .


Interleukin-8 ( IL-8 ) is a chemokine that belongs to the alpha-chemokine or CXC subfamily and is produced by a wide variety of human cells , including monocytes and polymorphonuclear cells ( PMN ) .

<protein>Interleukin-8</protein> ( <protein>IL-8</protein> ) is a <protein>chemokine</protein> that belongs to the <protein>alpha-chemokine</protein> or <protein>CXC subfamily</protein> and is produced by a wide variety of human cells , including <cell_type>monocytes</cell_type> and <cell_type>polymorphonuclear cells</cell_type> ( <cell_type>PMN</cell_type> ) .


IL-8 is secreted in response to inflammatory stimuli , notably bacterial products such as lipopolysaccharide ( LPS ) , but little is known about the mechanisms by which these agents mediate IL-8 induction .

<protein>IL-8</protein> is secreted in response to inflammatory stimuli , notably bacterial products such as lipopolysaccharide ( LPS ) , but little is known about the mechanisms by which these agents mediate <protein>IL-8</protein> induction .


In this report , we show that Mycoplasma fermentans lipid-associated membrane proteins ( LAMPf ) induce the production of high levels of IL-8 by THP-1 ( human monocyte ) cells and PMN at the same extent as LPS .

In this report , we show that <protein>Mycoplasma fermentans lipid-associated membrane proteins</protein> ( <protein>LAMPf</protein> ) induce the production of high levels of <protein>IL-8</protein> by <cell_line>THP-1 ( human monocyte ) cells</cell_line> and <cell_type>PMN</cell_type> at the same extent as LPS .


It was previously demonstrated that stimulation of monocytic cells with either LPS or LAMPf led to a series of common downstream signaling events , including the activation of protein tyrosine kinase and of mitogen-activated protein kinase cascades .

It was previously demonstrated that stimulation of monocytic cells with either LPS or <protein>LAMPf</protein> led to a series of common downstream signaling events , including the activation of <protein>protein tyrosine kinase</protein> and of <protein>mitogen-activated protein kinase</protein> cascades .


By using PD-98059 and SB203580 , two potent and selective inhibitors of MEK1 ( a kinase upstream of ERK1/2 ) and p38 , respectively , we have demonstrated that both ERK1/2 and p38 cascades play a key role in the production of IL-8 by monocytes and PMN stimulated with bacterial fractions .

By using PD-98059 and SB203580 , two potent and selective inhibitors of <protein>MEK1</protein> ( a <protein>kinase</protein> upstream of <protein>ERK1/2</protein> ) and <protein>p38</protein> , respectively , we have demonstrated that both ERK1/2 and p38 cascades play a key role in the production of <protein>IL-8</protein> by <cell_type>monocytes</cell_type> and <cell_type>PMN</cell_type> stimulated with bacterial fractions .


Regulation of IL-6 synthesis in human peripheral blood mononuclear cells by C3a and C3a ( desArg ) .

Regulation of <protein>IL-6</protein> synthesis in <cell_type>human peripheral blood mononuclear cells</cell_type> by <protein>C3a</protein> and <protein>C3a ( desArg )</protein> .


The anaphylatoxin C3a has been reported to have immunomodulatory effects on a number of different cell types .

The <protein>anaphylatoxin</protein> <protein>C3a</protein> has been reported to have immunomodulatory effects on a number of different cell types .


In this study we investigated the effects of C3a and C3a ( desArg ) on gene expression and protein secretion of IL-6 in human PBMCs , either alone or in combination with LPS or IL-1beta .

In this study we investigated the effects of <protein>C3a</protein> and <protein>C3a ( desArg )</protein> on gene expression and protein secretion of <protein>IL-6</protein> in human <cell_type>PBMCs</cell_type> , either alone or in combination with LPS or <protein>IL-1beta</protein> .


C3a or C3a ( desArg ) alone exhibited no effect on the expression or secretion of IL-6 .

<protein>C3a</protein> or <protein>C3a ( desArg )</protein> alone exhibited no effect on the expression or secretion of <protein>IL-6</protein> .


However , when PBMC were stimulated with LPS or IL-1beta , both C3a and C3a ( desArg ) were found to enhance IL-6 release by PBMC in a dose-dependent manner .

However , when <cell_type>PBMC</cell_type> were stimulated with LPS or <protein>IL-1beta</protein> , both <protein>C3a</protein> and <protein>C3a ( desArg )</protein> were found to enhance <protein>IL-6</protein> release by <cell_type>PBMC</cell_type> in a dose-dependent manner .


Since C3a has been shown to induce PGE2 production by monocytes , and PGE2 has been shown to influence cytokine production , we investigated the potential role of PGE2 in C3a -mediated enhancement of LPS- and IL-1beta-induced IL-6 production .

Since <protein>C3a</protein> has been shown to induce PGE2 production by <cell_type>monocytes</cell_type> , and PGE2 has been shown to influence cytokine production , we investigated the potential role of PGE2 in <protein>C3a</protein> -mediated enhancement of LPS- and IL-1beta-induced IL-6 production .


Indomethacin blocked PGE2 release , but had no influence on the observed effects of C3a , suggesting that the effects of C3a on IL-6 production are independent of PGE2 formation by monocytes .

Indomethacin blocked PGE2 release , but had no influence on the observed effects of <protein>C3a</protein> , suggesting that the effects of <protein>C3a</protein> on <protein>IL-6</protein> production are independent of PGE2 formation by <cell_type>monocytes</cell_type> .


Northern blot analysis showed that C3a as well as C3a ( desArg ) enhanced LPS -induced mRNA levels for IL-6 .

Northern blot analysis showed that <protein>C3a</protein> as well as <protein>C3a ( desArg )</protein> enhanced LPS <rna>-induced mRNA</rna> levels for <protein>IL-6</protein> .


Pretreatment of PBMCs with pertussis toxin blocked the functions of C3a and C3a ( desArg ) , indicating that the actions of these two molecules are mediated by a G protein -coupled pathway .

Pretreatment of <cell_type>PBMCs</cell_type> with <protein>pertussis toxin</protein> blocked the functions of <protein>C3a</protein> and <protein>C3a ( desArg )</protein> , indicating that the actions of these two molecules are mediated by a <protein>G protein</protein> -coupled pathway .


Furthermore , we investigated the effects of C3a and C3a ( desArg ) on induction of NF-kappaB and activating protein-1 binding .

Furthermore , we investigated the effects of <protein>C3a</protein> and <protein>C3a ( desArg )</protein> on induction of <protein>NF-kappaB</protein> and <protein>activating protein-1</protein> binding .


Both molecules enhanced LPS-induced NF-kappaB and activating protein-1 binding activity .

Both molecules enhanced LPS-induced <protein>NF-kappaB</protein> and <protein>activating protein-1</protein> binding activity .


These results demonstrate the capacity of intact C3a and its circulating des-Arg form to exert immunmodulatory effects in vitro .

These results demonstrate the capacity of intact <protein>C3a</protein> and its circulating <protein>des-Arg form</protein> to exert immunmodulatory effects in vitro .


Phenylarsine oxide inhibits ex vivo HIV-1 expression .


Phenylarsine oxide ( PAO ) , which is described as an inhibitor of tyrosine phosphatase activity , inhibits H2O2 release from human peripheral blood mononuclear cells ( PBMCs ) as measured by electrochemistry .

Phenylarsine oxide ( PAO ) , which is described as an inhibitor of <protein>tyrosine phosphatase</protein> activity , inhibits H2O2 release from <cell_type>human peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) as measured by electrochemistry .


Since human immunodeficiency virus type 1 ( HIV-1 ) replication is known to be favored under oxidative stress conditions , ex vivo experiments using uninfected PBMCs , primary monocytes or a latently infected promonocytic U1 cell line show that HIV-1 replication and reactivation , monitored by p24 antigen measurement , are inhibited by PAO in a time- and concentration-dependent manner .

Since human immunodeficiency virus type 1 ( HIV-1 ) replication is known to be favored under oxidative stress conditions , ex vivo experiments using uninfected <cell_type>PBMCs</cell_type> , <cell_type>primary monocytes</cell_type> or a latently infected <cell_line>promonocytic U1 cell line</cell_line> show that HIV-1 replication and reactivation , monitored by <protein>p24 antigen</protein> measurement , are inhibited by PAO in a time- and concentration-dependent manner .


These observations can be linked with the inhibition of NF-kappa B activation when uninfected monocytes are induced by either tumor necrosis factor alpha ( TNF-alpha ) phorbol 12-myristate 13-acetate ( PMA ) or lipopolysaccharide ( LPS ) .

These observations can be linked with the inhibition of <protein>NF-kappa B</protein> activation when uninfected monocytes are induced by either <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) phorbol 12-myristate 13-acetate ( PMA ) or lipopolysaccharide ( LPS ) .


Pharmacological control of antigen responsiveness in genetically modified T lymphocytes .

Pharmacological control of antigen responsiveness in <cell_line>genetically modified T lymphocytes</cell_line> .


A chimeric TCR gene , comprising an anti-hapten single-chain Ab variable fragment fused to the transmembrane and cytoplasmic regions of the human TCR zeta-chain , was used to determine whether the tetracycline-regulatable system could be used to regulate gene expression in T cells .

A <dna>chimeric TCR gene</dna> , comprising an <protein>anti-hapten single-chain Ab variable fragment</protein> fused to the <protein>transmembrane and cytoplasmic regions</protein> of the <protein>human TCR zeta-chain</protein> , was used to determine whether the tetracycline-regulatable system could be used to regulate gene expression in <cell_type>T cells</cell_type> .


Jurkat T cells were stably transfected with a single vector encoding the tetracycline trans-activator protein , controlled by a constitutive promoter , and the chimeric TCR , under the control of a trans-activator protein-responsive promoter .

<cell_line>Jurkat T cells</cell_line> were stably transfected with a single vector encoding the <protein>tetracycline trans-activator protein</protein> , controlled by a <dna>constitutive promoter</dna> , and the <protein>chimeric TCR</protein> , under the control of a <dna>trans-activator protein-responsive promoter</dna> .


In the absence of tetracyclines , the transfected T cells were shown to express the chimeric receptor on the cell surface and could be activated by its cognate Ag , leading to the secretion of IL-2 .

In the absence of tetracyclines , the transfected <cell_type>T cells</cell_type> were shown to express the <protein>chimeric receptor</protein> on the cell surface and could be activated by its <protein>cognate Ag</protein> , leading to the secretion of <protein>IL-2</protein> .


When the cells were exposed to increasing concentrations of tetracyclines , surface expression of the chimeric receptor was suppressed in a dose-dependent manner , and this suppression was sufficient to result in complete loss of responsiveness to the targeted Ag .

When the cells were exposed to increasing concentrations of tetracyclines , surface expression of the <protein>chimeric receptor</protein> was suppressed in a dose-dependent manner , and this suppression was sufficient to result in complete loss of responsiveness to the <protein>targeted Ag</protein> .


Prolonged suppression of trans-gene expression for up to 7 days was observed after doxycycline was removed from the cultures , but eventual recovery of surface expression was complete , and the absolute time to recovery was directly proportional to the initial concentration of the drug .


Pharmacologic control of trans-gene expression in gene-modified T cells will not only facilitate new approaches to the study of different aspects of T cell biology , but will also provide the basis for new gene therapy strategies .

Pharmacologic control of trans-gene expression in <cell_line>gene-modified T cells</cell_line> will not only facilitate new approaches to the study of different aspects of T cell biology , but will also provide the basis for new gene therapy strategies .


Glucocorticoid receptors , fibromyalgia and low back pain .

<protein>Glucocorticoid receptors</protein> , fibromyalgia and low back pain .


Recently , fibromyalgia ( FMS ) was shown to be a disorder associated with an altered functioning of the stress response system .


FMS patients display a hyperreactive pituitary adrenocorticotropic hormone ( ACTH ) release in response to corticotropin-releasing hormone ( CRH ) and to insulin-induced hypoglycemia .


We suggested that negative feedback of cortisol could be deranged .


Therefore we investigated the properties and function of the glucocorticoid receptors ( GR ) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain ( LBP a localized pain condition ) .

Therefore we investigated the properties and function of the <protein>glucocorticoid receptors</protein> ( <protein>GR</protein> ) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain ( LBP a localized pain condition ) .


Forty primary FMS patients ( F : M = 36 : 4 ) , 28 LBP patients ( 25 : 3 ) and 14 ( 12 : 2 ) healthy , sedentary control persons were recruited for the study .


Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls .


Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls .


However , plasma free cortisol concentrations were similar in the three groups .


There was no difference in the number of GR per cell among the three groups ( FMS : 6498 +/- 252 , LBP : 6625 +/- 284 , controls : 6576 +/- 304 ) , but the dissociation constant ( Kd ) of the FMS ( 14.5 +/- 0.9 nmol/l ) and LBP ( 14.7 +/- 1.3 nmol/l ) subjects was significantly higher than that of the controls ( 10.9 +/- 0.8 nmol/l ) ( p < .05 ) .

There was no difference in the number of <protein>GR</protein> per cell among the three groups ( FMS : 6498 +/- 252 , LBP : 6625 +/- 284 , controls : 6576 +/- 304 ) , but the dissociation constant ( Kd ) of the FMS ( 14.5 +/- 0.9 nmol/l ) and LBP ( 14.7 +/- 1.3 nmol/l ) subjects was significantly higher than that of the controls ( 10.9 +/- 0.8 nmol/l ) ( p < .05 ) .


The maximal stimulation of the lymphocytes , as measured by the maximal thymidine incorporation ( in the absence of cortisol ) in the FMS group was approximately 1.5 times higher ( p < .05 ) than in the control or LBP group .

The maximal stimulation of the <cell_type>lymphocytes</cell_type> , as measured by the maximal thymidine incorporation ( in the absence of cortisol ) in the FMS group was approximately 1.5 times higher ( p < .05 ) than in the control or LBP group .


The ED50 ( the cortisol concentration giving 50 % inhibition of the thymidine incorporation ) , however , was identical in all three groups .


We conclude that FMS patients have a mild hypocortisolemia , increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus .


The role of the GR and mineralocorticoid receptor ( MR ) in the CRH regulation in the FMS patients remains to be solved .

The role of the <protein>GR</protein> and <protein>mineralocorticoid receptor</protein> ( <protein>MR</protein> ) in the CRH regulation in the FMS patients remains to be solved .


Temporal control of IgH gene expression in developing B cells by the 3 ' locus control region .

Temporal control of <dna>IgH gene</dna> expression in <cell_type>developing B cells</cell_type> by the <dna>3 ' locus control region</dna> .