Suppression of autophagy sensitizes Kupffer cells to endotoxin

Hepatology Research : the Official Journal of the Japan Society of Hepatology
Hiroo FukadaSumio Watanabe

Abstract

Recent evidence suggests that protein degradation system autophagy is implicated in a component of innate immunity. We report here that suppression of autophagy in Kupffer cells due to hepatic steatosis enhances an inflammatory response to endotoxin. Kupffer cells were isolated from C57BL/6J mice fed chow diet (control) or high-fat diet (HFD) for 12 weeks, liver-specific autophagy-deficient mice (Atg7(F/F) :Mx1-Cre) and wild-type mice (Atg7(F/F) ). Kupffer cells were incubated with 100 ng/mL lipopolysaccharide (LPS). The concentration of tumor necrosis factor (TNF)-α in media was measured by enzyme-linked immunoassay. Expression of Toll-like receptor (TLR)4, IκB kinase (IKK)-α/β, p38, p62 and LC3 in Kupffer cells was evaluated by western blot analysis. Incubation with LPS increased LC3-II expression of Kupffer cells from control mice; however, an increase in LC3-II expression due to LPS was suppressed in Kupffer cells from HFD mice. Moreover, both p62 expression and TNF-α production in Kupffer cells from HFD mice was higher than control mice. On the other hand, LPS exposure increased TNF-α production from autophagy-deficient Kupffer cells more than wild type. There was no significant difference in expression of TLR4 between wil...Continue Reading

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Citations

Aug 24, 2013·PloS One·Wei-qun ZengZuo-jin Liu
Dec 5, 2013·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Yuka FukuoSumio Watanabe
Apr 7, 2016·Autophagy·Gustav van NiekerkAnna-Mart Engelbrecht
Feb 25, 2017·Advanced Healthcare Materials·Shasha ZhuLongping Wen
Dec 5, 2019·Frontiers in Immunology·Andrea Kristina HorstLinda Diehl
Jan 21, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Steven A Bloomer, Eric D Moyer
May 13, 2021·International Journal of Hepatology·Suryakant NitureDeepak Kumar

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