title: Butyrate mediates nucleotide-binding and oligomerisation domain (NOD) 2-dependent mucosal immune responses against peptidoglycan.
abstract: The interaction between digestive tract microbiological flora and food has an important influence on human health. Butyrate is produced during the fermentation of dietary fibres by intestinal bacteria and plays an important role in the regulation of mucosal immunity. In this report, we studied the impact of butyrate on the defence mechanism against the bacterial membrane component peptidoglycan (PGN). Butyrate was found to enhance PGN-mediated IL-8 and GRO-alpha production. The expression of these chemokines required the activation of NF-kappaB and was dependent on the concentrations of butyrate and PGN. Butyrate was found to up-regulate nucleotide-binding and oligomerisation domain (NOD) 2, but not NOD1 or TLR2. NOD2 up-regulation was mediated by an increase in histone acetylation in the Nod2 promoter region, leading to enhanced PGN-induced IL-8 and GRO-alpha secretion. Knockdown of NOD2 and TLR2 by siRNA significantly reduced PGN-mediated chemokine production, suggesting that both NOD2 and TLR2 are required for maximal response. Our findings provide a better understanding of the mechanism by which butyrate regulates mucosal immunity for normal intestinal function. Based on the results of this study, we infer that dietary fibres can impact inflammatory bowel diseases.
authors.affiliation: The Open Laboratory of Chemical Biology of Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Chemistry, The University of Hong Kong, Hong Kong. duncanl@hku.hk
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
authors.forename: Wing
authors.initials: W
authors.lastname: Lam
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Gullen
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology*; D018938:Caco-2 Cells; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002087:Butyrates; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D018925:Chemokines; D016209:Interleukin-8; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; D051195:Toll-Like Receptor 2