Mycotoxin Patulin Suppresses Innate Immune Responses by Mitochondrial Dysfunction and p62/Sequestosome-1-dependent Mitophagy
Journal
The Journal of biological chemistry
Journal Volume
291
Journal Issue
37
Pages
19299
Date Issued
2016
Author(s)
Tsai, Wan-Ting
Lo, Yin-Chiu
Wu, Ming-Sian
Li, Chia-Yang
Kuo, Yi-Ping
Lai, Yi-Hui
Tsai, Yu
Chen, Kai-Chieh
Chuang, Tsung-Hsien
Yao, Chun-Hsu
Lee, Jinq-Chyi
Hsu, John T-A
Yu, Guann-Yi
Abstract
Innate immune responses are important for pathogen elimination and adaptive immune response activation. However, excess inflammation may contribute to immunopathology and disease progression (e.g. inflammation-associated hepatocellular carcinoma). Immune modulation resulting from pattern recognition receptor-induced responses is a potential strategy for controlling immunopathology and related diseases. This study demonstrates that the mycotoxin patulin suppresses Toll-like receptor- and RIG-I/MAVS-dependent cytokine production through GSH depletion, mitochondrial dysfunction, the activation of p62-associated mitophagy, and p62-TRAF6 interaction. Blockade of autophagy restored the immunosuppressive activity of patulin, and pharmacological activation of p62-dependent mitophagy directly reduced RIG-I-like receptor-dependent inflammatory cytokine production. These results demonstrated that p62-dependent mitophagy has an immunosuppressive role to innate immune response and might serve as a potential immunomodulatory target for inflammation-associated diseases.
Subjects
RIG-I-like receptor (RLR); immunomodulation; mitochondria; mitophagy; mycotoxin; p62 (sequestosome 1(SQSTM1)); patulin; toll-like receptor (TLR)
SDGs
Other Subjects
Chemical activation; Pathology; Pattern recognition; Adaptive immune response; Cytokine production; Disease progression; Hepatocellular carcinoma; Innate immune response; Mitochondrial dysfunction; Pattern recognition receptors; Toll-like receptors; Immune system; cytokine; glutathione; patulin; protein p62; receptor; retinoic acid inducible protein I; RIG I like receptor; toll like receptor; tumor necrosis factor receptor associated factor 6; unclassified drug; mycotoxin; patulin; sequestosome 1; SQSTM1 protein, human; Sqstm1 protein, mouse; animal cell; animal experiment; Article; autophagy; cell stimulation; controlled study; cytokine production; disease association; disorders of mitochondrial functions; human; human cell; immune deficiency; immunomodulation; immunopathogenesis; inflammation; innate immunity; mitophagy; mouse; nonhuman; priority journal; protein depletion; protein function; protein protein interaction; animal; drug effects; HEK293 cell line; immunology; innate immunity; mitophagy; RAW 264.7 cell line; Animals; HEK293 Cells; Humans; Immunity, Innate; Mice; Mitochondrial Degradation; Mycotoxins; Patulin; RAW 264.7 Cells; Sequestosome-1 Protein
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Type
journal article