Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease development

Oncotarget
Kun HeJian-Ping Gong

Abstract

NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1β (IL-1β) secretion in Kupffer cells (KCs). However, the specific mechanism of the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3 on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP-/- (thioredoxin-interacting protein) and NLRP3-/- mice, and isolated KCs. We found that the expressions of NLRP3 and TXNIP in human liver tissues were higher in NASH group than in NAFL group. Furthermore, co-immunoprecipitation analyses show that activation of the TXNIP-NLRP3 inflammasome protein complex occurred in KCs of NASH WT mice rather than NAFL WT mice, thus suggesting that the formation and activation of this protein complex is mainly involved in the development of NASH. NLRP3-/- mice exhibited less severe NASH than WT mice...Continue Reading

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Citations

Jun 12, 2020·Seminars in Liver Disease·Jana KnorrAriel E Feldstein
Jul 22, 2020·Molecular Nutrition & Food Research·Maria WallertStefan Lorkowski
Sep 15, 2018·International Journal of Molecular Sciences·Katrin NeumannGisa Tiegs
Sep 29, 2020·Frontiers in Immunology·Tabassum RahmanJonathan A Harton
Oct 10, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Axelle CooremanMathieu Vinken
Jan 24, 2019·Laboratory animal research·Ji-Young ChaKyung-Hee Chun
Apr 19, 2020·International Immunopharmacology·Abdullah Al MamunJian Xiao
Dec 4, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Wenqi YangLiangming Li

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Methods Mentioned

BETA
transmission electron microscopy
Co-IP
confocal microscopy
Protein Assay
electrophoresis
co-immunoprecipitation
Assay

Software Mentioned

SPSS
Maxquant

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