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

Our present study was designed to clarify the mechanism by which the same megakaryocyte progenitor cells respond to various cytokines at different stages of megakaryocyte development. We examined the changes in mRNA expression of granulocyte macrophage colony-stimulating factor receptor beta-subunit (GM-CSFR beta-subunit), which was a common subunit of a high-affinity interleukin-3 receptor (IL-3R) and a high-affinity GM-CSFR, and interleukin-6 receptor (IL-6R) during megakaryocyte development in a human megakaryocytic leukemia cell line (CMK) which could proliferate and/or differentiate in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, GM-CSF, and IL-6. We found that GM-CSFR beta-subunit mRNA was expressed constitutively in CMK cells and was transiently down-regulated by TPA and IL-6, while the expression of IL-6R mRNA was increased by TPA in association with the differentiation of megakaryocytes. Furthermore, the TPA-induced down-regulation of GM-CSFR beta-subunit mRNA expression and its recovery were blocked by cycloheximide (CHX), a protein synthesis inhibitor, suggesting that these modulations required de novo protein synthesis. These findings imply that multi-lineage cytokines such as GM-CSF and IL-3 may contribute preferentially to the regulation of the earlier development of megakaryocyte progenitor cells with high densities of multi-lineage cytokine receptors, while IL-6 may be limited in its action to supporting the maturation of more differentiated megakaryocyte progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of GM-CSF receptor beta-subunit and interleukin-6 receptor mRNA expression in a human megakaryocytic leukemia cell line. 129 Sep 64

Metalloproteinases and their specific inhibitors, believed to play a role in extracellular matrix metabolism, are regulated by inflammatory cytokines. Here we have addressed the question of whether liver, the major site of synthesis of plasma proteinase inhibitors, is also capable of synthesizing the tissue inhibitor of metalloproteinase-1 (TIMP-1). We show at mRNA and protein levels that TIMP-1 is expressed in differentiated human hepatoma cells (HepG2) and that its synthesis is up-regulated by interleukin-6 (IL-6), transforming growth factor beta 1 and phorbol 12-myristate 13-acetate. The physiological role of this phenomenon is underlined by the fact that lipopolysaccharide administration into rats in vivo, as well as IL-6-stimulation of rat hepatocytes in primary culture, also leads to an increase of TIMP-1 mRNA in liver cells.
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PMID:Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in human hepatoma cells (HepG2). Up-regulation by interleukin-6 and transforming growth factor beta 1. 133 Jul 2

Transcription of interleukin-6 (IL-6) gene in human HepG2 and HeLa cells was induced by treatment with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), phorbol 12-myristate 13-acetate, or dibutyryl cyclic AMP. These agents enhanced the expression of chloramphenicol acetyltransferase (CAT) activity in cells transfected with chimeric CAT genes driven by the transcriptional regulatory regions of human IL-6 gene. Both induced and basal levels of CAT expression were severely repressed upon co-transfection of expression vectors encoding the adenoviral E1A289R or E1A243R protein. The conserved region 1 of E1A proteins was required for this activity. IL-6-CAT expression could also be induced by co-transfecting expression vectors containing cDNAs of the catalytic subunit of protein kinase A or c-jun. E1A repressed transcriptional induction by these agents as well. Similar inhibition was observed when a CAT gene driven by the NF kappa B element of the IL-6 gene was used as a reporter plasmid. In a cell line stably transfected with the E1A gene, IL-1 or TNF-alpha failed to induce IL-6 mRNA. Electrophoretic mobility shift assays were carried out with nuclear extracts of these cells using, as probes, the NF kappa B element or the multiple regulatory element of the IL-6 gene. With either probe, additional faster migrating DNA-protein complexes were formed in the extracts of E1A-expressing cells as compared with the extracts of the corresponding control cells. Experiments with NF kappa B antibody revealed differences between the different DNA-protein complexes formed in the extract of E1A-expressing cells. These observations suggest that E1A represses IL-6 gene transcription by interfering with the formation of appropriate DNA-protein complexes.
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PMID:Transcriptional repression of interleukin-6 gene by adenoviral E1A proteins. 133 71

Epstein-Barr virus (EBV)-induced in vitro infection of peripheral blood mononuclear cells (PBMCs) leads to a polyclonal proliferation and immortalisation of B lymphocytes. In the present study we determined the effects of three different cytokines, interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), and the tumour promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on EBV-immortalised B lymphocytes. These factors have known activities on normal B cells. IL-4 and IL-6 increased significantly EBV-B cell proliferation after 3 and 5 days of culture, where IL-2 had no effect. The effect of IL-4 and IL-6 on EBV-B cells was abolished after pre-incubation with anti-IL-4 and anti-IL-6 neutralising antisera, respectively. TPA induced a dose dependent inhibition of proliferation both in serum free and 10% fetal calf serum (FCS) supplemented culture medium. Combinations of TPA and interleukins did not restore lymphoblastoid cell proliferation to background levels. All possible combinations of the three cytokines showed no synergistic or antagonistic effect on proliferation. TPA induced significant phenotypic changes of EBV immortalised B lymphocytes, by increasing IL-2 receptor (IL-2R) expression and decreasing CD20 and CD23 antigen expression. Other B cell differentiation antigens; HLA-DR, CD19, and transferrin receptor (CD71), did not demonstrate significant changes. A dose dependent inhibition of CD21 and increase in CD22 expression was observed in 2 out of 3 lymphoblastoid cell lines tested.
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PMID:Effects of phorbol esters and cytokines (interleukin-2,-4, and -6) on the proliferation and surface phenotype of Epstein-Barr virus immortalised human B lymphocytes. 133 96

The expression of 80 kDa interleukin-6 receptor (IL-6R) and the associated molecule gp130 has been studied on human cell lines by FACS- and Northern blot analysis. The effects of dexamethasone, dibutyric-(DB)-cAMP and phorbol-12-myristate-13-acetate (TPA) have been studied on plasmacytoma cell line U266, B cell line BMNH and monocytoid cell line U937. Our data show a definite downregulation of IL-6R and gp130 expression by TPA in U266 and BMNH at both mRNA and cell surface protein levels. In U937 TPA inhibits only the IL-6R expression, without affecting that of gp130. DB-cAMP decreases the expression of both proteins in U937, slightly inhibits the IL-6R expression in U266, but is uneffective in BMNH. Dexamethasone induces considerable upregulation of gp130 only in U266. Our findings suggest separate regulation of IL-6R and gp130 on U266, BMNH and U937 cell lines.
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PMID:Regulation of IL-6 receptor and gp130 expression on human cell lines of lymphoid and myeloid origin. 133 86

Okadaic acid, a phosphatase inhibitor from a marine organism, mimics tumor necrosis factor/interleukin-1 (TNF/IL-1) in inducing changes in early cellular protein phosphorylation. A total of approximately 116 proteins exhibit significant and concordant changes in phosphorylation or dephosphorylation within 15 min in human fibroblasts activated by either okadaic acid, TNF, or IL-1. The fidelity of this mimicry by okadaic acid extends to the phosphorylation of the 27 hsp complex, stathmin, eIF-4E, myosin light chain, nucleolin, epidermal growth factor receptor, and other cdc2-kinase substrates (c-abl, RB, and p53). The okadaic acid-induced pattern of protein phosphorylation is distinct from that observed in cells treated with phorbol 12-myristate 13-acetate or with ligands like epidermal growth factor, cyclic AMP agonists, bradykinin, or interferons. Like TNF, okadaic acid also induces the transcription of immediate early response genes like c-jun and Egr-1 as well as the interleukin-6 genes. The overall early effects of okadaic acid uniquely parallel those of TNF/IL-1 and not those of other cytokines or ligands. Regulation of protein phosphatase inhibition is discussed as a mechanism for TNF/IL-1 signal transduction.
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PMID:Okadaic acid mimics multiple changes in early protein phosphorylation and gene expression induced by tumor necrosis factor or interleukin-1. 137 Apr 82

The effect of murine IgG isotypes on the gene expression and secretion of the third component of complement (C3) has been studied using the monocytoid cell line P388D1 and oil-elicited mouse peritoneal macrophages. It is demonstrated that the binding of IgG2a and IgG2b but not IgG1 and IgG3 augments the biosynthesis of C3 both in the presence and in the absence of the phorbol ester, phorbol myristate acetate in the case of both cell types. The multifunctional cytokine interleukin-6 (IL-6) alone reveals no effect on the gene expression of C3, but increases the effectiveness of mouse IgG2a and IgG2b. Confirming the role of Fc gamma RII, a strong up-regulation of C3 gene expression and C3 secretion was found when macrophages were cultured with the F(ab')2 fragment of the Fc gamma RII-specific monoclonal antibody 2.4G2.
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PMID:Fc gamma R-dependent regulation of the biosynthesis of complement C3 by murine macrophages: the modulatory effect of IL-6. 137 Nov 92

We examined the expression of interleukin-6 (IL-6) by 12 established human melanoma cell lines. Two constitutively produced low levels of IL-6 protein, as measured by enzyme-linked immunosorbent assay. Cells from these two lines, as well as those from two non-IL-6-producing cell lines, contained IL-6-specific mRNA as demonstrated by Northern hybridization. Treatment of the two IL-6-producing melanoma cell lines with interleukin-1 beta, tumor necrosis factor-alpha, or phorbol myristate acetate caused a marked increase in IL-6 production. These induction signals failed to stimulate IL-6 production in the nonproducing cells, even those that expressed IL-6 mRNA. IL-6 did not appear to act as an autocrine growth factor since the addition of exogenous human recombinant IL-6 or polyclonal anti-IL-6 antibody did not alter cellular proliferation. The production of this multifunctional cytokine by tumors may play a role in tumor-host interactions and this should be recognized in the design of biologic therapy trials.
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PMID:Interleukin-6 production by human melanoma cell lines. 139 Dec 35

Apoptosis of neutrophils at sites of inflammation in vivo is thought to lead to their recognition and safe elimination by macrophages. Little is known, however, about the regulation of apoptosis in myeloid cells. We report here that the human promonocytic leukemic cell line, U937, and mature human neutrophils can be induced to become apoptotic when cultured with interleukin-6. Apoptosis of U937 cells, assessed morphologically and by the presence of DNA fragmentation, was increased significantly in a dose-dependent fashion by concentrations of 0.5-100 ng/ml interleukin-6. Apoptosis of U937 cells was evident after 48 h of incubation with 20 ng/ml interleukin-6, and the effect was eliminated by adsorption of interleukin-6 with a specific monoclonal antibody. Apoptosis was not evident in the presence of the differentiating agent phorbol 12-myristate 13 acetate; the induction of apoptosis in U937 cells was not therefore a consequence of differentiation. Apoptosis of mature neutrophils was enhanced after 24 h in culture with interleukin-6. Interleukin-6 might be an important factor in the normal resolution of inflammation through the induction of apoptosis of neutrophils.
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PMID:The induction by human interleukin-6 of apoptosis in the promonocytic cell line U937 and human neutrophils. 140 Apr 72

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the proliferation of lymphocytes and on the production of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) was examined in normal human peripheral blood mononuclear cells (PBMC) activated in vitro either by phytohaemagglutinin (PHA) or by the monoclonal antibody to the T-cell receptor OKT3, or by the combination of each of these two stimuli with phorbol myristate acetate (PMA). 1,25(OH)2D3 inhibited the proliferative response of PBMC to PHA; this effect, however, was abrogated by the addition of PMA (1.6 nM), and it was reversed from inhibition to stimulation by higher concentrations of the phorbol ester. In contrast to the PHA-activated cells, 1,25(OH)2D3 had no effect on the proliferative response of PBMC to OKT3. Further, 1,25(OH)2D3 inhibited the release of IL-6 in cultures of PHA-activated PBMC, whereas it stimulated IL-6 with the addition of PMA in these cultures. In contrast to the PHA-activated cells, 1,25(OH)2D3 increased IL-6 release in OKT3-activated cells. IL-1 beta production was not affected in either PHA- or OKT3-activated cells by the presence of the hormone, but it was stimulated by 1,25(OH)2D3 when PMA was used as a co-stimulus with either PHA or OKT3. Finally, 1,25(OH)2D3 inhibited IFN-gamma in both PHA- and OKT3-activated cells, but these effects were attenuated in the presence of PMA. These findings demonstrate that the in vitro effects of 1,25(OH)2D3 on lymphocyte proliferation and cytokine production by PBMC are pleiotropic, and that such pleiotropism depends upon the mode of PBMC activation and presumably the signals that are generated in response to the specific agents used to activate these cells.
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PMID:Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters. 149 24


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