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Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4.
Venkatesh, Madhukumar; Mukherjee, Subhajit; Wang, Hongwei; Li, Hao; Sun, Katherine; Benechet, Alexandre P; Qiu, Zhijuan; Maher, Leigh; Redinbo, Matthew R; Phillips, Robert S; Fleet, James C; Kortagere, Sandhya; Mukherjee, Paromita; Fasano, Alessio; Le Ven, Jessica; Nicholson, Jeremy K; Dumas, Marc E; Khanna, Kamal M; Mani, Sridhar.
Afiliação
  • Venkatesh M; Departments of Genetics and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Mukherjee S; Departments of Genetics and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Wang H; Departments of Genetics and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Li H; Departments of Genetics and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Sun K; Department of Pathology, Montefiore Medical Center, Bronx, NY 10467, USA.
  • Benechet AP; Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
  • Qiu Z; Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
  • Maher L; Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
  • Redinbo MR; Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Phillips RS; Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • Fleet JC; Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
  • Kortagere S; Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
  • Mukherjee P; Departments of Genetics and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Fasano A; Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA.
  • Le Ven J; Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
  • Nicholson JK; Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
  • Dumas ME; Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
  • Khanna KM; Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA. Electronic address: kkhanna@uchc.edu.
  • Mani S; Departments of Genetics and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: sridhar.mani@einstein.yu.edu.
Immunity ; 41(2): 296-310, 2014 Aug 21.
Article em En | MEDLINE | ID: mdl-25065623
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Esteroides / Junções Íntimas / Receptor 4 Toll-Like / Intestinos Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Esteroides / Junções Íntimas / Receptor 4 Toll-Like / Intestinos Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article