کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8292580 1536733 2018 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Roseburia intestinalis-derived flagellin is a negative regulator of intestinal inflammation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Roseburia intestinalis-derived flagellin is a negative regulator of intestinal inflammation
چکیده انگلیسی
Our previous study showed that the Roseburia intestinalis (R. intestinalis), one of the dominant intestinal bacterial microbiota, was significantly decreased in Crohn's disease patients and protected colon epithelial cells from inflammatory damage. However, the roles of lncRNAs in R. intestinalis flagellin-mediated anti-inflammation remain unclear. In this study, we investigate global lncRNA expression profiles using microarray analysis of ulcerative colitis samples from DSS/Flagellin-challenged mice and identified a Flagellin-induced upregulated lncRNA (HIF1A-AS2). Flagellin induced HIF1A-AS2 expression in a dose- and time-dependent manner via p38-stat1 activation. Selective pharmacological inhibitors of Stat1 and p38, and genetic knockdown of these genes abolished Flagellin-induced HIF1A-AS2 expression. In addition, luciferase reporter assay showed that Flagellin activated HIF1A-AS2 promotor via increasing stat1 phosphorylation. Silencing of HIF1A-AS2 abolished Flagellin-mediated anti-inflammatory effects, evaluating by upregulation of cytokines expression, including TNF-α, IL-1β, IL-6 and IL-12, but not TNFβ. In addition, knockdown of HIF1A-AS2 significantly increased p65 and Jnk phosphorylation, and sufficiently abolished Flagellin-mediated anti-inflammatory affects in vivo. Our study provides new insights into the mechanisms that lncRNAs regulate flagellin-mediated alleviation of colonic inflammation. It is indicated that HIF1A-AS2 may be a modulator of intestinal inflammation and represent a novel target for future therapeutics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 501, Issue 3, 27 June 2018, Pages 791-799
نویسندگان
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