NDLI: Xenobiotic pregnane X receptor (PXR) regulates innate immunity via activation of NLRP3 inflammasome in vascular endothelial cells.

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Xenobiotic pregnane X receptor (PXR) regulates innate immunity via activation of NLRP3 inflammasome in vascular endothelial cells.

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Xenobiotic pregnane X receptor (PXR) regulates innate immunity via activation of NLRP3 inflammasome in vascular endothelial cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lai, Baochang Wang, Shaolan Zhang, Kang Fang, Li Lei, Ting Wang, Nanping Han, Jie Xiao, Lei Zhao, Wenxiang
Description	Author Affiliation: Wang S ( From the Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an 710061 and.); Lei T ( From the Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an 710061 and.); Zhang K ( From the Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an 710061 and.); Zhao W ( From the Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an 710061 and.); Fang L ( Institute of Cardiovascular Science, Peking University, Beijing 100191, China.); Lai B ( From the Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an 710061 and.); Han J ( From the Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an 710061 and.); Xiao L ( From the Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an 710061 and.); Wang N ( From the Cardiovascular Research Center, School of Medicine, Xi'an Jiaotong University, Xi'an 710061 and Institute of Cardiovascular Science, Peking University, Beijing 100191, China nanpingwang2003@yahoo.com.)
Abstract	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-1ß (IL-1ß). 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.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	43
Volume Number	289
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2014-10-24
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carrier Proteins Metabolism Endothelial Cells Immunity, Innate Inflammasomes Receptors, Steroid Xenobiotics Amino Acid Sequence Animals Binding Sites Genetics Gene Expression Regulation Gene Knockdown Techniques Hep G2 Cells Human Umbilical Vein Endothelial Cells Molecular Sequence Data Receptors, Pattern Recognition Agonists Antagonists & Inhibitors Response Elements Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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