کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6107442 1211173 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ArticleHepatitis B virus X protein stimulates IL-6 expression in hepatocytes via a MyD88-dependent pathway
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Research ArticleHepatitis B virus X protein stimulates IL-6 expression in hepatocytes via a MyD88-dependent pathway
چکیده انگلیسی

Background & AimsHepatitis B virus (HBV) X protein (HBx) has been implicated in HBV-associated carcinogenesis by activating signal transduction pathways and influencing gene transcription in liver cells. We aimed to investigate the underlying mechanisms for HBx-induced production of interleukin-6 (IL-6), one of the major inflammatory mediators that stimulate hepatocellular carcinoma development.MethodsHBx was overexpressed in hepatic and hepatoma cell lines and IL-6 expression levels were measured by quantitative RT-PCR and ELISA. The activation of IRAK-1, ERKs/p38, and NF-κB was determined by Western blotting using specific anti-phosphoprotein antibodies. The role of MyD88 in these processes was analyzed by MyD88 RNAi and expression of an inactive MyD88 mutant.ResultsExpression of HBx in hepatic and hepatoma cells led to a dramatic enhancement of IL-6 synthesis and secretion. Dysfunction of MyD88 in these cells prevented the HBx-triggered IL-6 production. HBx expression also activated downstream signaling proteins of MyD88 including IRAK-1, ERKs/p38, and NF-κB. Inactivation of these signaling molecules blocked IL-6 synthesis as well. HBx-stimulated the expression of MyD88.ConclusionsIn hepatocytes and hepatoma cells, HBx stimulates the production of IL-6 in a MyD88-dependent manner, indicating that parenchymal liver cells are an additional source of high levels of IL-6 in the HBV-infected liver microenvironment. HBx could be involved in HBV-mediated liver carcinogenesis, through this mechanism of action.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 54, Issue 1, January 2011, Pages 26-33
نویسندگان
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