Butyrate mediates nucleotide‐binding and oligomerisation domain (NOD) 2‐dependent mucosal immune responses against peptidoglycan
Copyright policy )Butyrate mediates nucleotide‐binding and oligomerisation domain (NOD) 2‐dependent mucosal immune responses against peptidoglycan
AbstractThe 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‐α production. The expression of these chemokines required the activation of NF‐κB 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‐α 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.
- University of Hong Kong China (People's Republic of)
- Yale University United States
- University of Hong Kong (香港大學) China (People's Republic of)
Mucosal - Drug Effects, Chemokine CXCL1, Blotting, Western, Nod2 Signaling Adaptor Protein, Peptidoglycan, Immunity, Mucosal - Drug Effects, Dose-Response Relationship, Chemokine Cxcl1 - Genetics - Metabolism, Nod1 Signaling Adaptor Protein, Humans, Immunity, Mucosal, Butyrates - Pharmacology, Rna Interference, Peptidoglycan - Pharmacology, Dose-Response Relationship, Drug, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Nod1 Signaling Adaptor Protein - Genetics - Metabolism, Interleukin-8, Immunity, NF-kappa B, Nf-Kappa B - Genetics - Metabolism, Toll-Like Receptor 2, Up-Regulation, Interleukin-8 - Genetics - Metabolism, Nod2 Signaling Adaptor Protein - Genetics - Metabolism, Butyrates, Chemokines - Metabolism - Secretion, Toll-Like Receptor 2 - Genetics - Metabolism, RNA Interference, Drug, Caco-2 Cells, Chemokines, Western, Up-Regulation - Drug Effects
Mucosal - Drug Effects, Chemokine CXCL1, Blotting, Western, Nod2 Signaling Adaptor Protein, Peptidoglycan, Immunity, Mucosal - Drug Effects, Dose-Response Relationship, Chemokine Cxcl1 - Genetics - Metabolism, Nod1 Signaling Adaptor Protein, Humans, Immunity, Mucosal, Butyrates - Pharmacology, Rna Interference, Peptidoglycan - Pharmacology, Dose-Response Relationship, Drug, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Nod1 Signaling Adaptor Protein - Genetics - Metabolism, Interleukin-8, Immunity, NF-kappa B, Nf-Kappa B - Genetics - Metabolism, Toll-Like Receptor 2, Up-Regulation, Interleukin-8 - Genetics - Metabolism, Nod2 Signaling Adaptor Protein - Genetics - Metabolism, Butyrates, Chemokines - Metabolism - Secretion, Toll-Like Receptor 2 - Genetics - Metabolism, RNA Interference, Drug, Caco-2 Cells, Chemokines, Western, Up-Regulation - Drug Effects
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