Roseburia intestinalis?derived flagellin ameliorates colitis by targeting miR?223?3p?mediated activation of NLRP3 inflammasome and pyroptosis.

ABSTRACT: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD), which is a chronic, relapsing condition associated with the disorder of gut microbial communities. A previous study reported that levels of Roseburia intestinalis (R.I), a butyrate?producing bacterium, are significantly decreased in patients with IBD and exert an anti?inflammatory function in dextran sulfate sodium (DSS)?induced colitis. However, the role of R.I flagellin in UC and its underlying molecular mechanism are not yet fully understood. Therefore, a DSS?induced colitis model in C57Bl/6 mice and the LPS/ATP?induced THP?1 macrophages were treated with R.I flagellin, which were used to investigate the anti?inflammatory effects of R.I flagellin. The results demonstrated that R.I flagellin decreased colitis?associated disease activity index, colonic shortening and the pathological damage of the colon tissues in murine colitis models. Furthermore, R.I flagellin decreased the serum levels of proinflammatory cytokines and inhibited activation of the nucleotide?binding oligomerization segment?like receptor family 3 (NLRP3) inflammasome in murine colitis. R.I flagellin was also demonstrated to decrease the Gasdermin D to yield the N?terminal fragment membrane pore and inhibit inflammasome?triggered pyroptosis. In vitro analysis indicated that microRNA (miR)?223?3p was involved in the regulation of R.I flagellin on NLRP3 inflammasome activation. Taken together, the results of the present study demonstrated that R.I flagellin inhibited activation of the NLRP3 inflammasome and pyroptosis via miR?223?3p/NLRP3 signaling in macrophages, suggesting that R.I flagellin may be used as a novel probiotic product for the treatment of UC.

SUBMITTER: Wu X 

PROVIDER: S-EPMC7453595 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature