Mycotoxin Patulin Suppresses Innate Immune Responses by Mitochondrial Dysfunction and p62/Sequestosome-1-dependent Mitophagy
| Autor: | John T.A. Hsu, Wan-Ting Tsai, Yu Tsai, Tsung-Hsien Chuang, Li-Chung Hsu, Kai-Chieh Chen, Ming-Sian Wu, Yin-Chiu Lo, Jinq-Chyi Lee, Chia-Yang Li, Guann-Yi Yu, Yi-Ping Kuo, Yi-Hui Lai, Chun-Hsu Yao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Inflammation Biology Biochemistry Mice 03 medical and health sciences Sequestosome 1 Immunopathology Sequestosome-1 Protein Mitophagy medicine Animals Humans education Molecular Biology education.field_of_study Innate immune system Autophagy Cell Biology Mycotoxins Acquired immune system Immunity Innate HEK293 Cells Patulin RAW 264.7 Cells 030104 developmental biology Cytokine Immunology medicine.symptom |
| Zdroj: | Journal of Biological Chemistry. 291:19299-19311 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.686683 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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