Colonic MUC2 mucin regulates the expression and antimicrobial activity of ?-defensin 2.

ABSTRACT: In this study we identified mechanisms at the colonic mucosa by which MUC2 mucin regulated the production of ?-defensin in a proinflammatory milieu but functionally protected susceptible bacteria from its antimicrobial effects. The regulator role of MUC2 on production of ?-defensin 2 in combination with the proinflammatory cytokine interleukin-1? (IL-1?) was confirmed using purified human colonic MUC2 mucin and colonic goblet cells short hairpin RNA (shRNA) silenced for MUC2. In vivo, Muc2(-/-) mice showed impaired ?-defensin mRNA expression and peptide localization in the colon as compared with Muc2(+/-) and Muc2(+/+) littermates. Importantly, purified MUC2 mucin abrogated the antimicrobial activity of ?-defensin 2 against nonpathogenic and enteropathogenic Escherichia coli. Sodium metaperiodate oxidation of MUC2 removed the capacity of MUC2 to stimulate ?-defensin production and MUC2's inhibition of defensin antimicrobial activity. This study highlights that a defective MUC2 mucin barrier, typical in inflammatory bowel diseases, may lead to deficient stimulation of ?-defensin 2 and an unbalanced microbiota that favor the growth of ?-defensin-resistant microbes such as Clostridium difficile.

SUBMITTER: Cobo ER 

PROVIDER: S-EPMC4762903 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other