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-a production. The expression of these chemokines required the activation of NF-jB 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-a secretion. Knockdown of NOD2 and TLR2 by siRNA significantly reduced PGNmediated 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.Key words: Butyrate . Intestinal immunity . Nucleotide-binding and oligomerization domains (NOD) .Peptidoglycan . TLR IntroductionIntestinal epithelial cells (IEC) function as a physical barrier against foreign substances in the intestinal lumen, such as food and pathogenic and non-pathogenic microorganisms. These cells are also involved in the host immune defence. Cytokines or chemokines are produced by IEC in response to potentially harmful substances, which are detected by a battery of pathogenrecognition receptors. These receptors are involved in the regulation of physiological and pathophysiological processes of the intestinal mucosa, including immunity and inflammation, via activation of MAPK and the key transcription factor, NF-kB [1][2][3][4]. The first widely studied family of receptors was the TLR family. Eleven mammalian TLR have been identified, of which TLR1-6 and TLR9 are expressed in IEC [3][4][5]. Another group of pathogenrecognition receptors, termed nucleotide-binding and oligomerisation domain (NOD) proteins, provide a second line of innate immune defence against bacterial infection. This family consists of more than 20 members and is located primarily in the cytosol. While NOD1 is constitutively expressed in IEC, the level of NOD2 expression is very low [1,2]. The bi-directional interaction between digestive tract microbiological flora and food has an important influence on human health, particularly on the immune response [6,7]. Butyrate is There is an increasing body of evidence demonstrating the importance of butyrate in maintaining intestinal mucosal immunity [9][10][11]. Butyrate has been shown to switch the transcriptional pattern of chemokine production through promotion of histone acetylation [12]. Several studies have also suggested...

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Antagonistic effect of peptidoglycan of Streptococcus sanguinis on lipopolysaccharide of major periodontal pathogens

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