کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2566948 1561086 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
RIP140 down-regulation alleviates acute lung injury via the inhibition of LPS-induced PPARγ promoter methylation
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی ریوی و تنفسی
پیش نمایش صفحه اول مقاله
RIP140 down-regulation alleviates acute lung injury via the inhibition of LPS-induced PPARγ promoter methylation
چکیده انگلیسی

Seriously inflammatory response of the lungs can induce acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) which are serious public health threats due to their high patient morbidity and mortality. While RIP140 is known to modulate proinflammatory cytokine production during an inflammatory response, its role in ALI/ARDS is unclear. In this study, we examined RIP140 and PPARγ protein expression in RAW 264.7 cells and lung tissue following LPS-induced ALI. RIP140 shRNA adenoviral knockdown significantly elevated PPARγ expression, inhibited TNF-α, IL-1β, and IL-6 production in vivo and in vitro. Conversely, treatment with a PPARγ antagonist (GW9662) reversed these outcomes. Furthermore, co-IP showed that endogenous and exogenous RIP140 interacted with DNMT3b in RAW 264.7 cells. Bisulfite conversion, pyrosequencing and activity assays demonstrated that PPARγ promoter methylation levels were increased and that PPARγ transcriptional activity was inhibited following LPS treatment in macrophages. Nevertheless, RIP140 knockdown reduced PPARγ promoter methylation levels and restored its transcriptional activity. These results indicate that RIP140 knockdown can inhibit the production of inflammation mediators and remit ALI via the repression of DNMT3b mediated PPARγ promoter methylation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pulmonary Pharmacology & Therapeutics - Volume 37, April 2016, Pages 57–64
نویسندگان
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