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IL-6 Induction (il-6 + induction)
Selected AbstractsOverload-induced skeletal muscle extracellular matrix remodelling and myofibre growth in mice lacking IL-6ACTA PHYSIOLOGICA, Issue 4 2009J. P. White Abstract Aim:, Overloading healthy skeletal muscle produces myofibre hypertrophy and extracellular matrix remodelling, and these processes are thought to be interdependent for producing muscle growth. Inflammatory cytokine interleukin-6 (IL-6) gene expression is induced in overloaded skeletal muscle, and the loss of this IL-6 induction can attenuate the hypertrophic response to overload (OV). Although the OV induction of IL-6 in skeletal muscle may be an important regulator of inflammatory processes and satellite cell proliferation, less is known about its role in the regulation of extracellular matrix remodelling. The purpose of the current study was to examine if OV-induced extracellular matrix remodelling, muscle growth, and associated gene expression were altered in mice that lack IL-6, when compared with wild-type mice. Methods:, Male C57/BL6 (WT) and C57/BL6 × IL-6,/, (IL-6,/,) mice (10 weeks of age) were assigned to either a sham control or synergist ablation OV treatments for 3, 21 or 56 days. Result:, Plantaris muscle mass increased 59% in WT and 116% in IL-6,/, mice after 21 day OV. Myofibre CSA was also increased by 21 day OV in both WT and IL-6,/, mice. OV induced a twofold greater increase in the volume of non-contractile tissue in IL-6,/, muscle compared to WT. OV also induced a significantly greater accumulation of hydroxyproline and procollagen-1 mRNA in IL-6,/, muscle, when compared with WT muscle after 21 day OV. Transforming growth factor-, and insulin-like growth factor-1 mRNA expression were also induced to a greater extent in IL-6,/, muscle when compared with WT muscle after 21 day OV. There was no effect of IL-6 loss on the induction of myogenin, and cyclin D1 mRNA expression after 3 day OV. However, MyoD mRNA expression in 3 day OV IL-6,/, muscle was attenuated when compared with WT OV mice. Conclusion:, IL-6 appears to be necessary for the normal regulation of extracellular matrix remodelling during OV-induced growth. [source] Interferon-, synergistically enhances induction of interleukin-6 by double stranded RNA in HeLa cellsFEBS JOURNAL, Issue 9 2000Jennifer L. Harcourt Double stranded RNA (dsRNA), an intermediate that is common during viral infection, directly induces much higher levels of expression of interleukin-6 (IL-6) mRNA than does the cytokine IL-1,. Interferon , (IFN,) by itself does not induce expression of IL-6; nonetheless, IFN, pretreatment dramatically enhances IL-6 induction by dsRNA but not by IL-1,. Mutation of either the activating transcription factor/cyclic AMP response element binding protein (ATF/CREB) or the NF-IL-6 binding element within the IL-6 promoter eliminates most responsiveness of CAT reporter constructs to either dsRNA or to IL-1,. IFN, pretreatment partially restores responsiveness to dsRNA but not to IL-1, when either the ATF/CREB site or the NF-IL-6 site is mutated, but at least one of these sites must be intact for responsiveness to be restored. Mutation of the ,B binding site in the IL-6 promoter eliminates responsiveness to either IL-1, or to dsRNA, and pretreatment with IFN, does not restore any responsiveness. Incubation with dsRNA leads to a decrease in protein translation, especially in cells that have been pretreated with IFN,. Nonetheless, IFN, pretreatment followed by dsRNA leads to very high IL-6 protein levels. These studies demonstrate that major differences exist in the induction of IL-6 at both the mRNA and protein levels by dsRNA compared to cytokines and that IFN, pretreatment selectively enhances IL-6 induction by dsRNA but not by IL-1,. The high levels of IL-6 expression that result when cells encounter class I IFN prior to dsRNA suggest a mechanism for a heightened host response to viral infection with heightened production of this pleotropic cytokine. [source] Interleukin-6 Induction by Helicobacter pylori in Human Macrophages is Dependent on PhagocytosisHELICOBACTER, Issue 3 2006Stefan Odenbreit Abstract Background:, The colonization of the gastric mucosa with Helicobacter pylori is accompanied by elevated levels of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and IL-8. The aim of our study was to determine the mechanisms of IL-6 stimulation in phagocytes upon H. pylori infection. Materials and Methods:, We investigated the secretion of IL-6 by different professional phagocytes from murine and human origin, including granulocyte- and monocyte-like cells and macrophages derived from human peripheral blood monocytes (PBMCs). The influence of viability, phagocytosis, and the impact of different subcellular fractions of H. pylori bacteria were evaluated. Results:, IL-6 levels induced by H. pylori were low in cell lines derived from murine and human monocytes and in human granulocyte-like cells. By contrast, macrophages derived from human PBMCs were highly responsive to both H. pylori and Escherichia coli. IL-6 induction was blocked by inhibition of actin-dependent processes prior to infection with H. pylori, but not with E. coli or E. coli lipopolysaccharide (LPS). Using cell fractionation, the most activity was found in the H. pylori membrane. H. pylori LPS exhibited a 103 - to 104 -fold lower biologic activity than E. coli LPS, suggesting a minor role for toll-like receptor 4 (TLR4)-mediated signalling from the exterior. Conclusions:, From these data, we conclude that macrophages may be a major source of IL-6 in the gastric mucosa upon H. pylori infection. The IL-6 induction by H. pylori in these cells is a multifactorial process, which requires the uptake and presumably degradation of H. pylori bacteria. [source] Increased Lipopolysaccharide Sensitivity in Alcoholic Fatty Livers Is Independent of Leptin Deficiency and Toll-Like Receptor 4 (TLR4) or TLR2 mRNA ExpressionALCOHOLISM, Issue 6 2005Laszlo Romics Jr Background: Both alcoholic (AFL) and nonalcoholic (NAFL) fatty livers show increased sensitivity to endotoxin-induced injury. Lipopolysaccharide (LPS) is recognized by toll-like receptor 4 (TLR4), whereas lipopeptide triggers TLR2 to induce common downstream activation of nuclear factor (NF)-,B and pro-inflammatory pathways that are activated in AFL and NAFL. Methods: Serum alanine aminotransferase (ALT), tumor necrosis factor (TNF)-,, and interleukin (IL)-6 levels; hepatic NF-,B activity; and expression of TLR2, TLR4, inducible nitric oxide synthase (iNOS), and heme oxygenase (HO)-1 mRNAs were investigated in lean and leptin-deficient ob/ob mice after LPS challenge in combination with acute or chronic alcohol feeding. Results: Increased LPS sensitivity in AFL and NAFL was characterized by elevated serum TNF-, and IL-6 induction. However, there was no difference in TLR2 and TLR4 mRNA levels between lean and ob/ob livers at baseline and after acute or chronic alcohol treatment. LPS increased TLR2, but not TLR4, mRNA levels in all groups. Chronic alcohol feeding and LPS increased serum ALT and TNF-, levels in lean but not in ob/ob mice compared with pair-fed controls. Hepatic NF-,B activation was increased in both ob/ob and lean mice after chronic alcohol feeding compared with pair-fed controls. Expression of iNOS, an inducer of oxidative stress, and HO-1, a cytoprotective protein, were higher in ob/ob compared with lean mice after chronic alcohol feeding. However, LPS-induced HO-1, but not iNOS, expression was attenuated in ob/ob compared with lean mice. Conclusion: These results imply that the increased sensitivity of AFL to LPS occurs without up-regulation of TLR2 or TLR4 genes and may be related to an imbalance of pro-inflammatory/oxidative and cytoprotective mechanisms. [source] | ||||||||||