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学科主题: 基础医学
题名:
Xenobiotic Pregnane X Receptor (PXR) Regulates Innate Immunity via Activation of NLRP3 Inflammasome in Vascular Endothelial Cells
作者: Wang, Shaolan1; Lei, Ting1; Zhang, Kang1; Zhao, Wenxiang1; Fang, Li2; Lai, Baochang1; Han, Jie1; Xiao, Lei1; Wang, Nanping1,2
关键词: Cellular Immune Response ; Endothelial Cell ; Innate Immunity ; Nod-like Receptor (NLR) ; Pattern Recognition Receptor (PRR) ; Toll-like Receptor (TLR) ; Transcription Factor ; Xenobiotic
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2014-10-24
DOI: 10.1074/jbc.M114.578781
卷: 289, 期:43, 页:30075-30081
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: DRUG-METABOLISM ; MACULAR DEGENERATION ; STRESS ; INFECTIONS ; DEFENSES ; PROMOTER ; DISEASE ; ELEMENT ; BINDING ; HEALTH
英文摘要:

Background: Xenobiotics activate nuclear receptor PXR for detoxification and clearance. However, a role of PXR in regulating innate immunity remains unknown. Results: PXR induced NLRP3 expression and triggered inflammasome activation in vascular ECs. Conclusion: PXR plays an important role in the activation of NLRP3 inflammasome in response to xenobiotics. Significance: Our findings revealed a novel mechanism of innate immunity.

Pregnane X receptor (PXR) is a member of nuclear receptor superfamily and responsible for the detoxification of xenobiotics. Our previously study demonstrated that PXR is expressed in endothelial cells (ECs) and acts as a master regulator of detoxification genes to protect ECs against xenobiotics. Vascular endothelial cells are key sentinel cells to sense the pathogens and xenobiotics. In this study, we examined the potential function of PXR in the regulation of innate immunity in vasculatures. Treatments with PXR agonists or overexpression of a constitutively active PXR in cultured ECs increased gene expression of the key pattern recognition receptors, including Toll-like receptors (TLR-2, -4, -9) and NOD-like receptors (NOD-1 and -2 and NLRP3). In particular, PXR agonism triggered the activation of NLRP3 inflammasome and the ensuing cleavage and maturation of caspase-1 and interleukin-1 (IL-1). Conversely, selective antagonism or gene silencing of PXR abrogated NLRP3 inflammasome activation. In addition, we identified NLRP3 as a transcriptional target of PXR by using the promoter-reporter and ChIP assays. In summary, our findings revealed a novel regulatory mechanism of innate immune by PXR, which may act as a master transcription factor controlling the convergence between the detoxification of xenobiotics and the innate immunity against them.

语种: 英语
所属项目编号: 81220108005 ; 31430045 ; 2010CB912502
项目资助者: National Science Foundation of China ; Ministry of Science and Technology
WOS记录号: WOS:000344370800047
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67290
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Xi An Jiao Tong Univ, Cardiovasc Res Ctr, Sch Med, Xian 710061, Peoples R China
2.Peking Univ, Inst Cardiovasc Sci, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Shaolan,Lei, Ting,Zhang, Kang,et al. Xenobiotic Pregnane X Receptor (PXR) Regulates Innate Immunity via Activation of NLRP3 Inflammasome in Vascular Endothelial Cells[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(43):30075-30081.
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