Xenobiotic Pregnane X Receptor (PXR) Regulates Innate Immunity via Activation of NLRP3 Inflammasome in Vascular Endothelial Cells

Abstract

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.

In vivo and systems biology studies implicate IL-18 as a central mediator in chronic pain

“…The inflammasome is a caspase-activating complex that serves critical roles in innate immunity (Franchi et al, 2009; Lechtenberg et al, 2014; Li et al, 2013; Schroder and Tschopp, 2010; Wang et al, 2014). It is known that inflammasome induction in macrophages leads to secretion of IL-18 as well as IL-1β.…”

Single Gene Inactivation with Implications to Diabetes and Multiple Organ Dysfunction Syndrome

“…Dysregulated Sirt 1 on adipocyte differentiation and senescence involves gene expression and secretion of adiponectin with effects [156,157]. Xenobiotics may nullify Sirt 1's role in NO homeostasis and vasodilation in the heart [85] with relevance to interference of therapeutic drugs for blood vessel dilation [158].…”

Higgs data constraints on the minimal supersymmetric standard model

“…Numerous activities occurred in the constraining the SM boson [3,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23], higher dimension operators of the Higgs boson [24][25][26][27][28][29], the two-Higgs doublet models [30][31][32][33][34][35][36][37][38][39][40][41][42][43], and in the supersymmetric framework [44][45][46][47][48][49][50][51][52][53]. A very recent update to all the data as of summer 2014 was performed in Ref.…”