Butyrate mediates nucleotide-binding and oligomerisation domain (NOD) 2-dependent mucosal immune responses against peptidoglycan

Chung-Hang Leung*, Wing Lam, Dik-Lung Ma, Elizabeth A. Gullen, Yung-Chi Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

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-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.
Original languageEnglish
Pages (from-to)3529-3537
Number of pages9
JournalEuropean Journal of Immunology
Volume39
Issue number12
DOIs
Publication statusPublished - Dec 2009

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

User-Defined Keywords

  • Butyrate
  • Intestinal immunity
  • Nucleotide-binding and oligomerization domains (NOD)
  • Peptidoglycan
  • TLR

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