Sok, Sophia P. M. and Ori, Daisuke and Wada, Ayana and Okude, Haruna and Kawasaki, Takumi and Momota, Masatoshi and Nagoor, Noor Hasima and Kawai, Taro (2021) 1 `-Acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression. International Immunology, 33 (7). pp. 373-386. ISSN 0953-8178, DOI https://doi.org/10.1093/intimm/dxab016.
Full text not available from this repository.Abstract
The nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing (NLRP) 3 inflammasome is a multiprotein complex that triggers Caspase-1-mediated IL-1 beta production and pyroptosis, and its dysregulation is associated with the pathogenesis of inflammatory diseases. 1'-Acetoxychavicol acetate (ACA) is a natural compound in the rhizome of tropical ginger Alpinia species with anti-microbial, anti-allergic and anti-cancer properties. In this study, we found that ACA suppressed NLRP3 inflammasome activation in mouse bone marrow-derived macrophages and human THP-1 monocytes. ACA inhibited Caspase-1 activation and IL-1 beta production by NLRP3 agonists such as nigericin, monosodium urate (MSU) crystals, and ATP. Moreover, it suppressed oligomerization of the adapter molecule, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1-mediated cleavage of pyroptosis executor Gasdermin D. Mechanistically, ACA inhibited generation of mitochondrial reactive oxygen species (ROS) and prevented release of oxidized mitochondrial DNA, which trigger NLRP3 inflammasome activation. ACA also prevented NLRP3 inflammasome activation in vivo, as evidenced in the MSU crystal-induced peritonitis and dextran sodium sulfate-induced colitis mouse models accompanied by decreased Caspase-1 activation. Thus, ACA is a potent inhibitor of the NLRP3 inflammasome for prevention of NLRP3-associated inflammatory diseases.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI)[17H04066], Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI)[20H03468] |
| Uncontrolled Keywords: | ACA;Macrophage;IL-1beta;mtROS;Ox-mtDNA |
| Subjects: | Q Science > Q Science (General) S Agriculture > S Agriculture (General) T Technology > T Technology (General) |
| Divisions: | Deputy Vice Chancellor (Research & Innovation) Office > Centre for Research in Biotechnology for Agriculture |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 22 Jul 2022 03:08 |
| Last Modified: | 22 Jul 2022 03:08 |
| URI: | http://eprints.um.edu.my/id/eprint/33913 |
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