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)

Interleukin-6 (IL6) is produced by different cell types, including monocytes and fibroblasts. We show that recombinant human IL6 (rhIL6) and chick fibroblast conditioned medium stimulate plasma fibronectin (PFn) and PFn mRNA production by cultured chick hepatocytes in a dose-dependent manner. Lipopolysaccharide (LPS) treatment of fibroblast cultures induces higher levels of the PFn stimulating activity. These effects are blocked by preincubation of either rhIL6 or LPS-stimulated chick fibroblast conditioned medium with anti-rhIL6 antibody before treatment of hepatocytes, indicating that the conditioned medium contains chick fibroblast-derived IL-6 (cfIL6). Further, LPS induces fibroblast production of a proportional increase in cfIL6 detectable by a human IL6 ELISA. cfIL6 maximally stimulates chick hepatocyte PFn production by 24 h (4.5-fold). Dexamethasone acts more rapidly, but maximal stimulation is only 2.3-fold. Hepatocyte Fn mRNA levels are even more substantially stimulated by dexamethasone and cfIL6 (up to 8.9- and 18.5-fold by 12 h, declining to 2.3 and 4.2-fold by 24 h, respectively). The effect cfIL6 with or without dexamethasone on hepatocyte PFn levels are comparable. These observations are consistent with the role of IL6 as a major mediator of acute phase protein production.
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PMID:Stimulation of chick hepatocyte fibronectin production by fibroblast-conditioned medium is due to interleukin 6. 768 98

Human airway epithelial cells play an active role in modulating airway inflammation by elaborating a variety of proinflammatory molecules, including cytokines. The purpose of this study was to define the role of corticosteroids in the regulation of cytokine gene transcription and secretion by human bronchial epithelial cells. In particular, we assessed whether dexamethasone was capable of inhibiting the tumor necrosis factor-alpha (TNF-alpha)-mediated secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte colony-stimulating factor (G-CSF) by a human bronchial epithelial cell line (BEAS-2B). Stimulation with 20 ng/ml of TNF-alpha resulted in significant increases in secretion of immunoreactive IL-6, IL-8, and G-CSF that were maximal at 24 h. TNF-alpha-mediated IL-6, IL-8, and G-CSF secretion was concentration dependent and specific. In addition, stimulation with TNF-alpha resulted in significant increases in the quantity of IL-6, IL-8, and G-CSF mRNA as detected by reverse-transcription polymerase chain reaction. Dexamethasone preconditioning significantly inhibited both the secretion of immunoreactive IL-6 and the accumulation of IL-6 mRNA. Although dexamethasone appeared to reduce both the secretion of immunoreactive IL-8 and accumulation of IL-8 mRNA, the inhibitory effects did not reach statistical significance. Finally, dexamethasone did not inhibit either the secretion of immunoreactive G-CSF or the accumulation of G-CSF mRNA. In summary, our results suggest that corticosteroids have a differential effect on the regulation of cytokine secretion by human bronchial epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Corticosteroids differentially regulate secretion of IL-6, IL-8, and G-CSF by a human bronchial epithelial cell line. 769 80

HepG2 cells were cultured for 7 days in serum-free medium in the presence of interleukin-6 (IL-6), retinoic acid (RA) or dexamethasone (DX), and some plasma proteins secreted to the media were determined by electroimmunoassay whereas the contents of specific mRNAs in the cells was evaluated by Northern blot hybridization. Interleukin-6 maximally stimulated synthesis of alpha-1-antichymotrypsin between days 1 and 3 whereas the response of fibrinogen was delayed to days 3 to 7. Retinoic acid increased the effect of IL-6 on alpha-1-antichymotrypsin (ACT) and fibrinogen (FBG) on the level of both proteins and mRNAs. Synthesis of albumin was slightly inhibited by IL-6 and RA, and synthesis of transferrin was increased by RA but not by IL-6. Dexamethasone had small enhancing effect on the action of IL-6. These results suggest that long-term HepG2 cultures may provide an experimental model for liver acute phase response during chronic inflammation.
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PMID:Long-term culture of HepG2 hepatoma cells as a model for liver acute phase response during chronic inflammation. Effects of interleukin-6, dexamethasone and retinoic acid. 769 40

Dexamethasone (sodium phosphate), pentoxifylline, fusidic acid (sodium salt), pentamidine (isethionate) and R-phenylisopropyladenosine (R-PIA) were tested for their anti-tumor necrosis factor (TNF) activities in an endotoxin-induced shock rat model. All the drugs reduced serum TNF concentrations in a dose-dependent manner, whereas their effects on serum interleukin-6 levels differed. Doses that reduced TNF levels by 50% were 0.012 mg/kg for dexamethasone, 0.06 mg/kg for R-PIA, 0.24 mg/kg for pentamidine, 6.5 mg/kg for fusidic acid and 15 mg/kg for pentoxifylline. Administration of the drugs to rats before intraplantar injection of carrageenan reduced paw edema by 50-70%. Injection of a monoclonal anti-TNF antibody reproduced the inhibitory effect. Moreover, the time course of tissue-associated TNF following carrageenan injection was compatible with mediation of edema by TNF. Results obtained for this acute, non-immunological inflammatory reaction strongly suggest that the model is TNF-dependent. Our results reinforce the idea that TNF is a crucial target in the therapeutics of inflammatory reactions. These drugs, which are able to cross cell barriers, might have clinical applications in localized and/or chronic diseases in which TNF is involved.
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PMID:Anti-tumor necrosis factor properties of non-peptide drugs in acute-phase responses. 770 32

In view of the immunosuppressive action of glucocorticoids (GCs), the activation of the hypothalamo-pituitary-adrenal axis in patients with sepsis or septic shock is paradoxical. At the same time, administration of GCs to these patients is not clearly beneficial. We investigated the role of GCs in severe illness by measuring the sensitivity of peripheral blood mononuclear leukocytes to GCs in a mitogen-stimulated lymphocyte proliferation assay. In addition, we studied the role of interleukin-2 and several other cytokines in this system. Cells from patients with sepsis or septic shock (n = 15) were more sensitive to the antiproliferative action of GCs than were cells from normal controls (IC50 6.7 +/- 2.1 nmol/L for patients vs. 19.5 +/- 2.5 nmol/L for controls; P < 0.01). This increased sensitivity of the peripheral mononuclear cells to dexamethasone during the period of sepsis normalized during the ensuing period of clinical recovery of these patients. Dexamethasone inhibited the production of interleukin-2 in the mitogen-stimulated cells. Addition of interleukin-2 antagonized the suppressive effects of dexamethasone in a dose-dependent manner, both in cells from controls and in cells from patients with sepsis. To a lesser extent, the combination of interleukin-1, interleukin-6, and tumor necrosis factor-alpha also counteracted the effects of dexamethasone. In conclusion, our results suggest that not only the activity of the hypothalamo-pituitary-adrenal axis but also the sensitivity to GCs is regulated during sepsis and septic shock. Generally there is an increased sensitivity to GCs, which might help to protect the organism as a whole through supportive effects on metabolism and vasculature. This hypersensitivity is counteracted, possibly at the site of inflammation, by high local concentrations of cytokines. This would enable an adequate local response of the immune system in the presence of elevated cortisol levels. In view of the increased sensitivity of peripheral leukocytes to GCs, treatment of these patients with high doses of GCs may not be beneficial or may even be harmful.
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PMID:Differential adaptation of glucocorticoid sensitivity of peripheral blood mononuclear leukocytes in patients with sepsis or septic shock. 777 26

Lipopolysaccharide (LPS)-binding protein (LBP) has been reported to be an acute-phase protein. LBP binds to LPS with a high affinity; LPS-LBP complexes then interact with the receptor CD14, resulting in increased expression of LPS-inducible genes. Hepatocytes represent a major source of LBP, but little is known about the regulation of rodent hepatocyte LBP synthesis. In these studies, undertaken to characterize hepatocyte LBP expression, we show that greater-than-20-fold increases in LBP mRNA levels in hepatocytes occurred following injection of LPS or turpentine in rats. In primary cultures of rat hepatocytes, the addition of interleukin-6 (IL-6) and LPS led to 4.5- and 3.2-fold stimulation in LBP mRNA levels, respectively. The induction of LBP by IL-6 or LPS was attenuated by dexamethasone. In contrast to IL-6 and LPS, in the presence of 10(-6) M dexamethasone, IL-1 and tumor necrosis factor (TNF) led to maximal LBP mRNA induction levels, 4.7- and 3.8-fold, respectively, suggesting that IL-6 and LPS stimulate LBP expression by mechanisms different from those of IL-1 and TNF. Similar induction levels of LBP mRNA were seen in rat H35 hepatoma cells for all four stimuli, and dexamethasone inhibited these responses. Dexamethasone alone increased the spontaneous induction in primary hepatocytes at early time points but suppressed induction at later time points. Furthermore, hepatocytes from rats treated with LPS in vivo exhibited a > 10-fold increase in mRNA expression in response to LPS and enhanced responses to TNF and IL-1. As with the normal hepatocytes, dexamethasone inhibited the LPS-dependent induction in the LPS-treated rat hepatocytes. These data suggest that LBP synthesis by hepatocytes is under the control of LPS, IL-1, TNF, IL-6, and glucocorticoids and that the LPS treatment primes hepatocytes for subsequent responses to LPS, TNF, and IL-1 for LBP synthesis.
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PMID:Role of lipopolysaccharide (LPS), interleukin-1, interleukin-6, tumor necrosis factor, and dexamethasone in regulation of LPS-binding protein expression in normal hepatocytes and hepatocytes from LPS-treated rats. 779 54

Interleukin-6 (IL-6) has been suggested as an autocrine growth factor of human renal cell carcinomas. Since steroids are known to inhibit IL-6 gene expression, we investigated their effects on the growth of renal cell carcinoma. Dexamethasone inhibited proliferation of 2 of 4 renal cell carcinoma cell lines in a dose-dependent manner. In one of these 2 cell lines, IL-6 gene expression was also inhibited, but not in the other. The inhibitory effect of dexamethasone on cell proliferation was not reversed by the exogenous IL-6. In 1 of the 2 remaining cell lines, the inhibition of IL-6 gene expression was observed, although there was no inhibition of cell proliferation. Thus, inhibition of growth by dexamethasone did not correlate with an inhibitory action of dexamethasone on IL-6 mRNA expression. Progesterone inhibited the growth of 1 cell line without concomitant inhibition of IL-6 gene expression. Expression of IL-6 receptor mRNA was not altered. A dose-dependent increase in mRNA expression of gp130, the transducer of IL-6 signal, was induced by dexamethasone and progesterone in 2 and 1 of the 4 cell lines, respectively. These data suggest that, in some renal cell carcinomas, steroids may inhibit cell proliferation by a mechanism independent of their effects on mRNA expression of IL-6 and IL-6 receptors. Dexamethasone may be useful, not only for palliation of paraneoplastic syndrome caused by overproduction of IL-6, but also for inhibition of growth of renal cell carcinomas.
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PMID:Inhibitory effect of dexamethasone and progesterone in vitro on proliferation of human renal cell carcinomas and effects on expression of interleukin-6 or interleukin-6 receptor. 786 51

Kupffer cells are known to produce tumor necrosis factor-alpha upon stimulation with endotoxin or viruses. This tumor necrosis factor-alpha synthesis is suppressed by prostaglandin E2 or dexamethasone. Using Northern blotting and reverse transcriptase-polymerase chain reaction, it is demonstrated that endotoxin-induced tumor necrosis factor-alpha synthesis is blocked by prostaglandin E2 or dibutyryl 3':5'-cyclic adenosine monophosphate on the transcriptional level. Tumor necrosis factor-alpha itself suppressed endotoxin-evoked tumor necrosis factor-alpha mRNA expression when given in a narrow time interval with lipopolysaccharide. Interleukin-10 of human or mouse origin also inhibited the synthesis of tumor necrosis factor-alpha mRNA and protein when given more than 2 h prior to the endotoxin challenge. The suppressive effect of prostaglandin E2 lasted for more than 36 h while IL-10 blocked tumor necrosis factor-alpha production for barely 24 h. Dexamethasone reduced the endotoxin-induced tumor necrosis factor-alpha mRNA formation by approximately 50% only, although it led to nearly complete inhibition of the synthesis of the mature protein. Taken together with reverse transcriptase-polymerase chain reaction data revealing significant amounts of tumor necrosis factor-alpha mRNA in resting Kupffer cells, an additional posttranscriptional regulation of tumor necrosis factor-alpha synthesis has to be assumed. Tumor necrosis factor-alpha mRNA was not induced by interferon-gamma, interleukin-1 beta or interleukin-6 (the latter two cytokines are also synthesized by Kupffer cells), but a 24-h prestimulation of liver macrophages with interferon-gamma or phorbol ester had a modest priming effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the mRNA expression for tumor necrosis factor-alpha in rat liver macrophages. 793 Apr 83

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine, which shares many characteristics with interleukin-6 (IL-6). Recent observations indicate a role for LIF in inflammatory processes. To examine the potential involvement of LIF in the regulation of mesangial cell behavior, we studied LIF expression in early primary cultures of rat and human mesangial cells, as well as the response of mesangial cells to exogenous LIF. Growing or growth-arrested rat mesangial cells constitutively expressed very low levels of LIF mRNA, barely detectable by Northern blot analysis. Strong induction of LIF mRNA expression was caused by cytokines, such as interleukin-1 beta (5 ng/ml), tumor necrosis factor alpha (100 ng/ml) and PDGF (100 ng/ml), as well as LPS (200 ng/ml). The induction was transient with a peak after three to five hours. Dexamethasone (0.1 microM) almost completely inhibited the induction of LIF. Weak induction of LIF mRNA was observed after stimulation with basic fibroblast growth factor, endothelin and transforming growth factor beta. In combination with IL-1 beta, TGF beta showed synergistic effects on LIF induction. LIF itself or IL-6 had no effect on LIF mRNA expression. A similar induction pattern was observed for the expression of IL-6 mRNA. LIF protein was detected by specific ELISA in the supernatants of human mesangial cells stimulated by LPS or IL-1 beta. In addition, we found that mesangial cells not only express LIF but they are also target cells for LIF. Recombinant LIF effectively induced transient expression of the immediate early genes, c-fos, jun-B and Egr-1 in rat mesangial cells, with a maximum at 30 to 60 minutes. LIF was not mitogenic for mesangial cells. Our findings indicate that glomerular mesangial cells produce and react to LIF. As a cytokine with autocrine potential, LIF may play a physiological and/or pathophysiological role in the glomerulus, the exact nature and relevance of which remain to be explored.
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PMID:Cytokine-induced expression of leukemia inhibitory factor in renal mesangial cells. 793 4

The effects of dexamethasone on the growth of four human multiple myeloma cell lines were studied. In addition, the effects on the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes were investigated by the use of reverse-transcriptase polymerase chain reaction. Dexamethasone (Dex) concentrations of 10(-7) to 10(-6) mol/L inhibited IL-6 gene expression in three of four cell lines studied, whereas the higher concentration of the hormone inhibited also IL-6R gene expression. Dex effects were modulated through the glucocorticoid receptor (GR). Dex treatment resulted in killing of sensitive cells associated with DNA fragmentation, which could be reversed by concomitant treatment with IL-6. The reversal of Dex-mediated effects by IL-6 did not result from an inhibition of GR function as measured by receptor nuclear translocation or Dex-regulated reporter gene function. These results indicate that blockage of the IL-6 signaling pathway is essential for effective myeloma cell kill by Dex.
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PMID:Interleukin-6 prevents dexamethasone-induced myeloma cell death. 794 78

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