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Xenobiotic Pregnane X Receptor (PXR) Regulates Innate Immunity via Activation of NLRP3 Inflammasome in Vascular Endothelial Cells
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
2014-10-24
DOI10.1074/jbc.M114.578781
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
资助者National Science Foundation of China ; Ministry of Science and Technology ; National Science Foundation of China ; Ministry of Science and Technology
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
资助者National Science Foundation of China ; Ministry of Science and Technology ; National Science Foundation of China ; Ministry of Science and Technology
WOS记录号WOS:000344370800047
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67290
专题基础医学院_心血管所
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
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GB/T 7714
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.
APA Wang, Shaolan.,Lei, Ting.,Zhang, Kang.,Zhao, Wenxiang.,Fang, Li.,...&Wang, Nanping.(2014).Xenobiotic Pregnane X Receptor (PXR) Regulates Innate Immunity via Activation of NLRP3 Inflammasome in Vascular Endothelial Cells.JOURNAL OF BIOLOGICAL CHEMISTRY,289(43),30075-30081.
MLA Wang, Shaolan,et al."Xenobiotic Pregnane X Receptor (PXR) Regulates Innate Immunity via Activation of NLRP3 Inflammasome in Vascular Endothelial Cells".JOURNAL OF BIOLOGICAL CHEMISTRY 289.43(2014):30075-30081.
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