| Literature DB >> 31177914 |
Subhash Mehto1, Swati Chauhan1, Kautilya Kumar Jena1,2, Nishant Ranjan Chauhan1, Parej Nath1,2, Rinku Sahu1, Kollori Dhar1, Saroj Kumar Das3, Santosh Chauhan1.
Abstract
IRGM is an established genetic risk factor for Crohn disease (CD) and several other inflammatory disorders. However, the mechanisms employed by IRGM to restrain the inflammation are not known. In our recent study, we showed that IRGM negatively regulates NLRP3 inflammasome activation. IRGM employs 2 parallel approaches to constrain inflammasome activation. First, IRGM directly interacts with NLRP3 and PYCARD/ASC, and mediates their SQSTM1/p62-dependent macroautophagic/autophagic degradation. Second, IRGM impedes inflammasome assembly by blocking the polymerization of NLRP3 and PYCARD. We also found that IRGM suppresses NLRP3-mediated exacerbated outcomes of dextran sodium sulfate (DSS)-induced colitis in a mouse model. Taken together, this study presents evidence that IRGM can directly regulate inflammation and protect from inflammatory diseases.Entities:
Keywords: Autophagy; Crohn disease; IRGM; IRGM1; NLRP3 inflammasome; inflammatory bowel disease
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Year: 2019 PMID： 31177914 PMCID： PMC6693461 DOI： 10.1080/15548627.2019.1628544
Source DB: PubMed Journal: Autophagy ISSN： 1554-8627 Impact factor: 16.016