| Literature DB >> 25065623 |
Madhukumar Venkatesh1, Subhajit Mukherjee1, Hongwei Wang1, Hao Li1, Katherine Sun2, Alexandre P Benechet3, Zhijuan Qiu3, Leigh Maher3, Matthew R Redinbo4, Robert S Phillips5, James C Fleet6, Sandhya Kortagere7, Paromita Mukherjee1, Alessio Fasano8, Jessica Le Ven9, Jeremy K Nicholson9, Marc E Dumas9, Kamal M Khanna10, Sridhar Mani11.
Abstract
Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2(-/-)) mice showed a distinctly "leaky" gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2(-/-)Tlr4(-/-) mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.Entities:
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Year: 2014 PMID： 25065623 PMCID： PMC4142105 DOI： 10.1016/j.immuni.2014.06.014
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745