UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipopolysaccharide (LPS) activates both myeloid and endothelial cells. Whereas CD14 has been shown to be involved in LPS recognition by myeloid cells, the mechanism responsible for the strong response of endothelial cells to LPS remains to be elucidated. The role of CD14 in this process was studied using CD14-specific antibodies (Ab). Anti-CD14 Ab inhibited LPS-induced interleukin-6 (IL-6) release and E-selectin expression by cultured human umbilical vein endothelial cells (HUVEC). Messenger RNA encoding IL-6 and E-selectin was reduced in parallel. The inhibitory effect of anti-CD14 Ab was epitope dependent, maximal at low LPS concentrations and dropping with increasing LPS doses. Anti-CD14 Ab did not affect endothelial cell activation induced by IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and phorbol 12-myristate 13-acetate (PMA). IL-6 release and E-selectin expression of HUVEC were strongly reduced when LPS activation was performed in the absence of serum, indicating involvement of serum components in LPS activation of HUVEC. Nevertheless, anti-CD14 Ab also blocked LPS-induced HUVEC activation in the absence of serum. Although the role of serum components in LPS activation remains to be elucidated, CD14 seems to be a key mediator in LPS-induced activation of endothelial cells.
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PMID:Anti-CD14 antibodies reduce responses of cultured human endothelial cells to endotoxin. 750 48

Production of interleukin-6 (IL-6) by the Th2 subset of murine T cells supposedly contributes to regulation of humoral immunity. Little information exists on IL-6 production by human T cells. We examined the requirements for IL-6 production by purified human blood T cells, completely depleted of IL-6-producing monocyte-accessory cells. Immobilized anti-CD3 mAb alone (coated on the culture wells) was unable to induce IL-6 production, although it could induce production of IL-2 and TNF-alpha. Addition of rIL-1 beta as an accessory signal to anti-CD3-stimulated human T cells induced IL-6 mRNA expression and protein secretion, while IL-2, IL-4, GM-CSF, IFN-gamma, or TNF-alpha did not have any effect. In the presence of IL-1 beta, both CD4+ and CD8+ T cells were able to produce IL-6. We also demonstrated that phorbol 12-myristate 13-acetate (PMA) or triggering of the CD28 molecule is an effective helper signal for IL-6 production by anti-CD3-stimulated T cells. Efficient CD28 ligation was done either by anti-CD28 mAb or by binding to its natural ligand B7/BB1, presented on the 3T6 mouse fibroblast cell line coexpressing transfected human Fc gamma RII (CD32) (to immobilize anti-CD3) and B7/BB1. Finally, we found that combinations of IL-1 beta with anti-CD28 mAb or PMA with anti-CD28 mAb were highly synergistic helper signals for IL-6 production. We conclude that IL-6 production by T cells is not induced by T cell receptor triggering alone, but different intracellular signaling pathways activated by IL-1 beta, CD28 ligation, or PMA efficiently coinduce IL-6 production.
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PMID:Interleukin-1 and B7/CD28 interaction regulate interleukin-6 production by human T cells. 750 12

An autograft of skeletal muscle on rat dorsal medulla is a permanent opening in the blood-brain barrier to solutes. Is the graft also a site for the entry of exogenous, isogeneic leukocytes? Five weeks after inserting the graft, peritoneal macrophages (M phi) from inbred Fischer rats were activated by phorbol myristate acetate, labeled with a fluorescent dye, and infused as a bolus of about 2 x 10(6) cells into the axillary artery of Fischer hosts. The cells circulated for 2 h. The brains were then fixed, frozen, and sectioned. Only when M phi had been activated and a muscle autograft inserted did appreciable numbers of M phi enter the medulla. Nonactivated M phi invaded the grafts but very few entered the brain at 2 h. In rats with gel foam grafts, only a few activated M phi invaded gel and brain. Before entering tissues, M phi must adhere to the lumenal face of vessels. Cell adhesion molecules, e.g., I-CAM-1 and its ligand adhesion molecule, leukocyte function antigen (LFA-1), are known to mediate adhesion. I-CAM-1, detected immunohistochemically, increased in graft vessels and in nearby brain vessels. The rise may have been mediated by cytokines, interleukin-6, and tumor necrosis factor-beta, found in the grafts. LFA-1, however, assayed by fluorescence-activated cell sorting, was on both activated and nonactivated, exogenous M phi. Thus, M phi-endothelial attachment may have involved other adhesion molecules, e.g., selectins. The autograft also induced major histocompatibility complex class I on microglia and classes I and II on brain vessels near the graft. These vessels, by expressing adhesion molecules, are entry routes into brain for activated, isogeneic leukocytes that can then migrate for a limited distance of 1-2 mm in an otherwise intact brain.
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PMID:Brain vessels near muscle autografts are sites for entry of isogeneic macrophages into brain. 750 59

Rapid transcriptional induction of genes in response to gamma interferon (IFN-gamma) is mediated by the IFN-gamma activation site (GAS) and its cognate protein, the IFN-gamma activation factor (GAF). We describe a GAS-associated, differentiation-induced factor (DIF) as a potential molecular link between the activities of IFN-gamma and of growth and differentiation factors. DIF DNA binding was activated by colony-stimulating factor 1 in murine macrophages and also during tetradecanoyl phorbol acetate-induced differentiation or IFN-gamma treatment in myeloid U937 cells. IFN-gamma activation of DIF decreased significantly upon monocytic differentiation. DIF binding to DNA was inhibited by antiphosphotyrosine antibodies and could be induced by treatment of U937 cells with vanadate. Unlike GAF, DIF-DNA complexes did not contain the 91-kDa protein (p91) from ISGF-3. DIF bound with high affinity to GAS from the promoters of the IFP 53/tryptophanyl-tRNA synthetase and Fc gamma RI genes, intermediate affinity to the Ly6A/E GAS, and low affinity to the guanylate-binding protein GAS. DIF may belong to a family of cytokine- or growth factor-induced factors binding with variable affinities to GAS-related elements: the interleukin-6-responsive acute-phase response factor associated with GAS from different IFN-inducible promoters but with a different preference of binding compared with DIF. The sis-inducible element of the c-fos promoter bound GAF but not DIF. However, the sis-inducible element could be changed by point mutation to compete for GAF and DIF binding. Our data show DIF to be a novel DNA-binding protein which is activated in response to differentiating signals. Moreover, they suggest that a family of cytokine- or growth factor-regulated proteins integrates and coordinates the responses to cytokines and to growth and differentiation factors by binding to GAS-related elements.
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PMID:A factor induced by differentiation signals in cells of the macrophage lineage binds to the gamma interferon activation site. 750 5

Recent evidence suggests that the level of interleukin-6 (IL-6) is elevated in Alzheimer's disease (AD) brains. IL-6 is produced by reactive glial cells and could potentially affect neuronal survival. Understanding the biochemical mechanism that regulates the production and release of IL-6 by astrocytic cells may help to identify potential targets for therapeutic intervention in AD. In the present study, glial fibrillary acidic protein-positive human U373MG astrocytoma cells were used as a model of reactive astrocytes. Production of IL-6 in response to drug treatment was monitored with an ELISA assay. Histamine (1-100 microM), substance P (SP; 1-100 nM), and human interleukin-1 beta (IL-1 beta; 1-30 pM) stimulated the release of IL-6 in a time- and concentration-dependent manner, with EC50 values of 4.5 microM, 8 nM, and 4.5 pM, respectively. The respective effects of histamine, SP, and IL-1 beta were effectively blocked by the histamine H1, SP, and IL-1 receptor antagonists, supporting a receptor-mediated event for these agents. Both histamine and SP enhanced the formation of inositol phosphates and increase intracellular calcium levels, suggesting that the phosphatidylinositol bisphosphate/protein kinase C pathway may be involved in the IL-6 release process. Indeed, phorbol 12-myristate 13-acetate, a protein kinase C activator, also evoked IL-6 release from the U373MG cells. On the other hand, IL-1 beta, which produces a much more robust release of IL-6 than histamine or SP, has no effect on inositol phosphate formation or intracellular calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the release of interleukin-6 from human astrocytoma cells. 751 68

Serum levels of alpha 1-antichymotrypsin (alpha 1-ACT) were measured in patients with early and late onset Alzheimer's disease (e-AD, 1-AD), patients with vascular dementia (VD) and healthy elderly. Patients with 1-AD were divided into two groups, one had normal alpha 1-ACT values and one had increased serum levels of alpha 1-ACT. Other acute phase proteins were also measured. The serum levels of alpha 2-macroglobulin (alpha 2-MG), alpha 1-antitrypsin (alpha 1-AT), ceruloplasmin (CER), transferrin (TRSF) and alpha 1-acid glycoprotein (alpha 1-ac.GL) were within the normal range. The C reactive protein (CRP) was occasionally detectable at low concentrations in e-AD, in both groups of 1-AD patients and in VD patients. Low serum concentrations of interleukin-6 (IL-6) were found in a higher proportion of 1-AD than in patients with e-AD or VD. These results indicated that increased levels of alpha 1-ACT along with occasional detection of IL-6 might be peripheral markers of the 'acute reaction' in the brain.
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PMID:Increased serum alpha 1-antichymotrypsin in patients with probable Alzheimer's disease: an acute phase reactant without the peripheral acute phase response. 753 91

The equilibrium denaturation of an Escherichia coli-derived recombinant murine interleukin-6 (mIL-6) was studied using fluorescence and circular dichroism spectroscopy. The urea-induced unfolding of mIL-6 at pH 4.0 can be described by a two-state unfolding mechanism based on the superimposibility of the CD and fluorescence unfolding transitions. Assuming a two-state mechanism and a linear dependence of the free energy of unfolding on denaturant concentration, a value of 6.9-9.0 kcal/mol was calculated for the free energy of unfolding in the absence of denaturant [delta GU(H2O)]. However, when GuHCl was used as a denaturant at pH 4.0, a biphasic unfolding transition was observed. This unfolding transition has a distinct midpoint occurring at 2.5 M GuHCl, which is indicative of the formation of stable folding intermediates. Similar intermediate folded species were also observed at pH 7.4 when either urea or GuHCl were used as denaturants. The intermediate folded states of mIL-6 exhibited a tendency to aggregate, as judged by the concentration dependence of their fluorescence characteristics. The fluorescence emission maximum of mIL-6 at pH 7.4 in the presence of 1.5 M GuHCl, for example, was blue-shifted from 343 nm at a protein concentration of 50 micrograms/mL to 336 nm at 500 micrograms/mL. Intermediate formation at pH 4.0, using 10 mM sodium acetate buffer and urea as the denaturant, was facilitated by the addition of 0.4 and 0.8 M salt, where the salt was either NaCl or GuHCl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Equilibrium denaturation of recombinant murine interleukin-6: effect of pH, denaturants, and salt on formation of folding intermediates. 754 97

There exist two distinct isozymes of prostaglandin-endoperoxide synthase (PES). PES-2 mRNA is synergistically induced by lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA) in bovine arterial endothelial cells. On the other hand, PES-1 mRNA is constitutively expressed under these conditions. Therefore, the promoter activities of the human genes for PES-1 and -2 in bovine arterial endothelial cells were examined. The 5'-flanking region of the human PES-2 gene (nucleotides -327 to +59) showed promoter activity inducible by LPS and TPA using transient transfection analysis, whereas that of the PES-1 gene (nucleotides -1010 to +69) showed constitutive promoter activity. Destruction of both consensus sequences for the nuclear factor responsible for the interleukin-6 expression (NF-IL6) site (nucleotides -132 to -124) and the cyclic AMP response element (CRE) (nucleotides -59 to -53) of the human PES-2 gene markedly reduced the promoter activity (25%) of the PES-2 gene after combined treatment with LPS and TPA, although single destruction of the NF-IL6 site or the CRE slightly reduced the promoter activity (60 or 90%, respectively). Moreover, cotransfection experiments showed that a trans-acting factor, CCAAT enhancer binding protein delta (C/EBP delta), which binds to both the NF-IL6 site and the CRE, increased the promoter activity of the PES-2 gene mainly through the CRE. C/EBP delta mRNA was rapidly induced by LPS. Collectively, these results suggest that transcription of the PES-2 gene in vascular endothelial cells is regulated through combination of the NF-IL6 site and the CRE and that C/EBP delta functions as one of the trans-acting factors.
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PMID:Transcriptional regulation of human prostaglandin-endoperoxide synthase-2 gene by lipopolysaccharide and phorbol ester in vascular endothelial cells. Involvement of both nuclear factor for interleukin-6 expression site and cAMP response element. 755 24

Both normal and leukaemic human megakaryocytopoiesis are stimulated by several cytokines, including stem cell factor, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3, GM-CSF/interleukin-3 fusion protein, interleukin-6, interleukin-11, basic fibroblast growth factor and thrombopoietin, but are inhibited by tumour necrosis factor-alpha, platelet factor 4, beta-thromboglobulin, thrombin, interleukin-4, interferon-alpha and interferon-gamma. Human megakaryoblastic leukaemia cell lines have common biological features, including high expression of the megakaryocytic specific antigen: CD41; high expression of the early myeloid antigens: CD34 and CD33; constitutive expression of interleukin-6 and platelet-derived growth factor; complex karyotype picture; expression of c-kit: the stem cell factor receptor; growth-dependency or -stimulation by stem cell factor, interleukin-3 and/or GM-CSF; megakaryoblastic differentiation by phorbol-myristate-acetate; and in vivo tumorigenicity in mice is associated with marked fibrosis. Only a few agents including phorbol-myristate-acetate; vitamin D3, interferon-alpha, interferon-beta 2, erythropoietin and thrombin have been reported to induce megakaryocytic differentiation in the human megakaryoblastic leukaemia cells.
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PMID:Characteristic biological features of human megakaryoblastic leukaemia cell lines. 756 68

Dendritic cells are the most potent antigen-presenting cells of the immune system. Although dendritic cells are likely to secrete selective cytokines that facilitate antigen presentation, the difficulty in isolating pure dendritic cells in sufficient numbers has made assessment of this function imprecise. In this study, pure populations of CD83+ human blood dendritic cells were isolated by previously established enrichment procedures and subsequent cell sorting. Cytokine gene expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA. Resting CD83+ dendritic cells expressed interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) mRNA, while activation of cells with phorbol myristate acetate induced IL-1 alpha and beta, IL-9, TNF-beta, interferon-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, and G-CSF mRNA expression. Resting CD83+ cells also expressed the Rantes, MCP-1, MIP-1 alpha, and MIP-1 beta chemokines, with 1-309 expression induced upon activation. Resting and activated CD83+ dendritic cells also expressed receptors for IL-2 (CD25), TGF-beta 1 and -beta 3, and GM-CSF as determined by indirect immunofluorescence staining. These results indicate that dendritic cells have the ability to produce a variety of soluble factors which are likely to contribute substantially to the potent allostimulatory activity of these cells.
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PMID:A distinct pattern of cytokine gene expression by human CD83+ blood dendritic cells. 757 30

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