期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 80, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2019.106144
关键词
Libertellenone M; Endophytic fungus; Anti-inflammatory; NLRP3 inflammasome; Experimental colitis
资金
- National Natural Science Foundation of China [81573446, 81974504]
- Natural Science Foundation of Jiangsu Province [BK20191251]
- Drug Innovation Major Project [2018ZX09711001-003-007]
NLRP3 inflammasome may serve as a potential target for the development of novel therapeutics for inflammatory bowel diseases. In this study, we found that Libertellenone M (Lib M), a secondary metabolite from the endophytic fungus Phomopsis sp. S12, has anti-inflammatory potential both in vitro and in vivo. Lib M selectively inhibited the expression of proinflammatory cytokine IL-1 beta and IL-18 in LPS-activated macrophages. The cleavage of pro-caspase 1 was remarkably reduced by Lib M in macrophages stimulated with three NLRP3 inflammasome activators. Administering Lib M attenuated dextran sulfate sodium-induced experimental acute colitis in mice and significantly reduced the production of these cytokines and cleaved caspase 1 in colon tissues. Apart from inhibition of NLRP3 inflammasome assembly, Lib M also suppressed NF-kappa B nuclear translocation in macrophages. Taken together, these findings suggest that Lib M-mediated inhibition of NLRP3 inflammasome activation could protect against colitis-like inflammatory diseases, and that this compound derived from a plant-associated fungus might inspire the exploration of novel immunosuppressive agents.
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