کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3314483 1211201 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytes
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytes
چکیده انگلیسی

Background/AimsHeme oxygenase-1 (HO-1) can be induced by various stimuli, one of which is interleukin-6 (IL-6). Therefore, the aim of this study was to elucidate the molecular mechanisms responsible for IL-6-dependent HO-1 induction in the liver.MethodsThe IL-6-dependent HO-1 regulation in rat primary hepatocytes and HepG2 hepatoma cells was studied by Northern and Western blot analyses, HO-1 promoter reporter gene assays and EMSA.ResultsThe HO-1 expression was transcriptionally induced by IL-6 in a time- and dose-dependent manner. Activation of signal transducers and activators of transcription (STAT) factors by the IL-6 receptor was crucial for HO-1 induction. By contrast, negative regulation of HO-1 expression appeared to be mediated through the SH2-domain-containing tyrosine phosphatase-2 (SHP2)/ suppressors of cytokine signaling-3 (SOCS3) binding site within the gp130 IL-6 receptor subunit. Among the three putative STAT binding elements (SBE) in the HO-1 promoter, only the distal one was functional and when deleted, the remaining Luc induction was completely obliterated by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002.ConclusionsThe HO-1 SBE3 mediates HO-1 gene induction by IL-6 mainly via activation of the Jak/STAT pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 45, Issue 1, July 2006, Pages 72–80
نویسندگان
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