| Literature DB >> 28893958 |
Leon Zheng1,2, Caleb J Kelly1,2, Kayla D Battista1,2, Rachel Schaefer1,2, Jordi M Lanis1,2, Erica E Alexeev1,2, Ruth X Wang1,2, Joseph C Onyiah1,2, Douglas J Kominsky3, Sean P Colgan4,2,5.
Abstract
Commensal interactions between the enteric microbiota and distal intestine play important roles in regulating human health. Short-chain fatty acids (SCFAs), such as butyrate, produced through anaerobic microbial metabolism represent a major energy source for the host colonic epithelium and enhance epithelial barrier function through unclear mechanisms. Separate studies revealed that the epithelial anti-inflammatory IL-10 receptor α subunit (IL-10RA) is also important for barrier formation. Based on these findings, we examined if SCFAs promote epithelial barrier through IL-10RA-dependent mechanisms. Using human intestinal epithelial cells (IECs), we discovered that SCFAs, particularly butyrate, enhanced IEC barrier formation, induced IL-10RA mRNA, IL-10RA protein, and transactivation through activated Stat3 and HDAC inhibition. Loss and gain of IL-10RA expression directly correlates with IEC barrier formation and butyrate represses permeability-promoting claudin-2 tight-junction protein expression through an IL-10RA-dependent mechanism. Our findings provide a novel mechanism by which microbial-derived butyrate promotes barrier through IL-10RA-dependent repression of claudin-2.Entities:
Mesh：
Substances：
Year: 2017 PMID： 28893958 PMCID： PMC5636678 DOI： 10.4049/jimmunol.1700105
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422