Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of several cytokines on des-gamma-carboxy prothrombin (PIVKA II) synthesis in human hepatoma cells were investigated to know the process of PIVKA II production during a liver allograft rejection. Human recombinant interleukin-6 (IL-6) significantly stimulated the PIVKA II synthesis without any influence on the cell proliferation. The effect was almost completely neutralized by the specific anti-IL-6 antibody. Neither tumor necrosis factor (TNF), interleukin-1 (IL-1) nor interferon-gamma (IFN-gamma) had such a stimulative effect. IL-6 appears to stimulate PIVKA II production, and would be a candidate of factors that enhance the production of PIVKA II during a liver allograft rejection.
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PMID:The effect of IL-6 on the des-gamma-carboxy prothrombin synthesis in human hepatoma cells. 133 90

C4b-binding protein (C4BP) is involved in the fluid-phase regulation of the classical pathway of complement. During an acute-phase response, we have shown that hepatic levels of murine C4BP mRNA are elevated 2.5-fold while rat liver C4BP gene expression exhibits a 4-fold induction. Furthermore, a survey of different mouse tissues showed that during acute inflammation C4BP gene expression was confined to the liver. To gain a better understanding of the acute-phase regulation of C4BP gene expression we utilized the rat hepatoma cell line FAO in which tumor necrosis factor-alpha (TNF-alpha) produced a 2.7-fold induction of C4BP mRNA levels. In the absence of TNF-alpha, interleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6) had little effect on C4BP gene expression but when all three cytokines were used together a synergistic 4-fold induction of C4BP mRNA levels was observed. In contrast the synthetic glucocorticoid dexamethasone inhibited TNF-alpha-induced C4BP gene expression. Cycloheximide-mediated inhibition of inducible C4BP gene expression demonstrated the requirement for ongoing protein synthesis. Rapid induction of C4BP mRNA levels by TNF-alpha and IL-6 (within 1 h) and the observation that stimulation was inhibited by actinomycin D provided evidence that regulation of C4BP gene expression during the acute-phase response is regulated at the transcriptional level. Isolation of a genomic clone extending into the 5' regulatory region of the rat C4BP gene enabled us to identify the major transcriptional start site and putative response elements through which TNF-alpha, IL-6, IL-1 alpha, and dexamethasone may exert their effects on C4BP gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of C4b-binding protein gene expression by the acute-phase mediators tumor necrosis factor-alpha, interleukin-6, and interleukin-1. 133 86

Prior studies on the in vitro hepatic acute phase response have involved either hepatoma cell lines or conventional short-term cultures of primary hepatocytes. No data are available on the response of primary hepatocytes in stable long-term culture systems. In this study, the acute phase response of rat and human hepatocytes in a new long-term culture system was examined in response to interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha). The cultured cells were sandwiched between two layers of collagen in a (double-gel) configuration which has been shown to preserve both hepatocyte function and morphology over prolonged periods of time. The stability of this culture configuration enabled us to investigate, for the first time, the temporal aspects of the response in addition to the effects of the mediators on protein secretion. Exposure of rat hepatocytes to IL-6 after culture for 16 days resulted in a 2-fold reduction of albumin secretion and a 15-fold increase in the secretion rates of fibrinogen and alpha 2-macroglobulin. In all instances, the peak response occurred at 48 h after IL-6 exposure, and all protein secretion rates returned to pretreatment values within 5 days posttreatment. Changes in the mRNA levels of these proteins in response to IL-6 corresponded with those changes seen with the secreted products, indicating pretranslational regulation. Administration of IL-1 beta to rat hepatocyte produced a similar decline of albumin secretion and a 5-fold increase of fibrinogen secretion, whereas alpha 2-macroglobulin secretion remained undisturbed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A stable long-term hepatocyte culture system for studies of physiologic processes: cytokine stimulation of the acute phase response in rat and human hepatocytes. 136 59

The effects of human interleukin-6 (hIL-6), the major acute-phase inducer, on the level of the transcript of microsomal heme oxygenase (HO) were examined in a human hepatoma cell line, Hep3B. Messenger RNAs (mRNAs) encoding HO and haptoglobin (Hpt) increased after hIL-6 treatment in a time- and dose-dependent manner. hIL-6 had no effect on the induction of heat-shock protein 70 (hsp70) mRNA, suggesting that the induction of HO by hIL-6 is regulated by a different mechanism from that which mediates the heat-shock induction of this enzyme. The hIL-6-mediated induction of HO mRNA was completely abrogated by simultaneous treatment of cells with actinomycin D, but not with cycloheximide, suggesting that the induction occurs at the level of transcription. A nuclear factor was shown both in untreated, and in the hIL-6-treated Hep3B cells that binds specifically to the IL-6-responsive element (IL6-RE) of the human HO gene. These findings suggest that HO is a positive acute-phase reactant in this human liver-derived cell line, and that the nuclear factor specific to the IL6-RE may be involved in the activation of the HO gene after hIL-6 treatment.
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PMID:Heme oxygenase is a positive acute-phase reactant in human Hep3B hepatoma cells. 137 18

The human hepatoma HuH-7 cell line was shown to constitutively express both a plasminogen activator (PA) and a plasminogen activator inhibitor (PAI). Four sublines of the HuH-7 cell line were analyzed and found to express differing amounts of both PA and PAI. The plasminogen activator produced by these cells was identified as urokinase based upon molecular weight, inhibition of activity with anti-UK but not anti-t-PA antibodies, adherence to an anti-UK affinity column and by Northern blotting demonstrating positive hybridization with the cDNA for UK, but not with the t-PA cDNA. The inhibitor produced by HuH-7 cells was identified as PAI-1 by molecular weight, immunoblotting techniques, adherence to an anti-PAI-1 affinity column, and by Northern blotting demonstrating positive hybridization with the cDNA for PAI-1, but not with the PAI-2 cDNA. The expression of both UK and PAI-1 by HuH-7 cells could be modulated by cytokines known to influence the acute phase response. The addition of interleukin-1 (IL-1) induced the expression of both UK and PAI-1. The increase of PAI-1 was due to an increase in amount of the PAI-1 mRNA. The presence of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) also increased UK and PAI-1 levels, although not as dramatically as IL-1. The addition of IL-1 together with IL-6 produced a slight synergistic response with respect to PAI-1 expression. This suggests that PAI-1 is able to respond to mediators which aid in the induction of the acute phase response. These studies demonstrate that cells of liver origin are able to produce components of the fibrinolytic system. The synthesis of these components can be altered by inflammatory mediators and thus may be involved in hepatic regulation of fibrinolysis in both normal and diseased states.
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PMID:Human HuH-7 hepatoma cells express urokinase and plasminogen activator inhibitor-1: identification, characterization and regulation by inflammatory mediators. 137 1

Effects of human interleukin-6 (hIL-6), the major acute phase inducer, on the expression of transcripts encoding cytochrome P450s were examined in human hepatoma-derived cells. Using reverse-transcription polymerase chain reaction, it was demonstrated that three hepatoma cell lines, HepG2, HepG2f and Hep3B, express P450 mRNAs encoding IA1, IA2 and IIIA3, the major P450 isozymes involved in carcinogen metabolism, and that they also show induction responses to treatment with their specific inducers. When hepatoma cells were treated with hIL-6, the levels of IA1, IA2 and IIIA3 mRNAs were markedly suppressed. These findings suggest that significant down regulation of cytochrome P450s may occur during the acute phase reaction, which may result in alterations in drug biotransformation.
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PMID:Interleukin-6 down regulates the expression of transcripts encoding cytochrome P450 IA1, IA2 and IIIA3 in human hepatoma cells. 137 45

We investigated the gene expression of the alpha chain of C4b-binding protein (C4bp alpha) in a variety of tissues, and in liver cell and hepatoma lines. C4bp alpha mRNA was detected in the liver, but not in the other tissues examined. The constitutive gene expression of C4bp alpha by a hepatoma line, HepG2, was significantly augmented by treatment with monocyte-conditioned medium (MoCM), 12-O-tetradecanoylphorbol-13-acetate (TPA), interleukin-6 (IL6) and tumor necrosis factor (TNF) but not by a calcium ionophore (A23187) or interleukin-1 beta (IL1 beta).
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PMID:Interleukin 6 and tumor necrosis factor fully activate liver-specific gene expression of the alpha chain of C4b-binding protein. 165 65

Interleukin-6 is a pleiotropic cytokine that has a major role in the coordination of the hepatic acute phase response. In order to more fully understand this role, we have examined the interleukin-6 induction of T kininogen, a cysteine protease inhibitor and a major acute phase reactant in the rat. Using deletional analysis and site-directed mutagenesis of T kininogen-chloramphenicol acetyltransferase fusion constructs transfected into HepG2 hepatoma cells, we have identified two similar interleukin-6 response elements within 250 base pairs of the transcription start site. These two response elements are functionally interdependent. The sequences of these two elements match the consensus sequence for the previously described Type B interleukin-6 response element. Interleukin-6 signal transduction via two Type B elements has not been observed previously in vivo. A DNA fragment encompassing these response elements forms the same protein complex with nuclear extracts from both untreated and interleukin-6-treated cells.
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PMID:Identification of sequences mediating interleukin-6 induction of a rat T kininogen gene. 165 51

We have studied the effect of interleukin-6 (IL-6) on the binding of tumor necrosis factor (TNF) to various cell lines. A significant increase (up to 250%) in binding was observed on rat hepatocytes and on the human hepatoma cell line HepG2, while no changes in the number of cells or cell morphology could be observed. Scatchard plot analysis showed that IL-6 enhanced the number of TNF receptors without affecting the receptor affinity. The effect reached plateau levels after approximately 6 h and at IL-6 concentrations of 10 ng/ml. It could be completely eliminated by cotreatment of cells with anti-IL-6 antibodies, but not by treatment with anti-interferon-gamma (IFN-gamma), suggesting that IFN-gamma, which can enhance TNF receptor expression on a variety of cells, was not a mediator in this IL-6 effect. Treatment with inhibitors of protein or RNA synthesis completely abolished the IL-6-induced increase, suggesting that IL-6 caused an enhanced transcription of TNF receptor mRNA. IL-1 had no effect on TNF binding to HepG2. However, when cells were cotreated with IL-1 and IL-6, IL-1 could completely abrogate the IL-6 effect.
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PMID:Interleukin-6 enhances the expression of tumor necrosis factor receptors on hepatoma cells and hepatocytes. 165 25

Ethanol alters many metabolic processes within the liver. Both ethanol abuse and the inability to mount an acute phase response (APR) have been associated with an increased morbidity and mortality in critically ill patients. To determine if ethanol influences the hepatic APR, relative amounts of two different human acute phase protein mRNA's were examined in the human hepatoma cell line Hep 3B before and after exposure to ethanol. Hep 3B cells were treated with one or more of the following: ethanol ((E) 150 mM); interleukin-1 beta ((IL-1) 200 units/ml); or interleukin-6 ((IL-6) 50 units/ml). After a 12-20 hr incubation relative amounts of mRNA for a1-protease inhibitor (PI) or beta fibrinogen were determined by Northern blot hybridization. Both ethanol and IL-6 were found to induce a1-PI mRNA. Fibrinogen mRNA was induced by IL-6 but not by ethanol, and no induction of PI or fibrinogen mRNA was found with IL-1. This suggests that under certain conditions, ethanol may influence acute phase protein metabolism. To our knowledge, this is the first description of an ethanol induced alteration of acute phase protein mRNA.
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PMID:Ethanol induces a1-protease inhibitor mRNA in Hep 3B cells. 165 92


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