Butyrate Switches the Pattern of Chemokine Secretion by Intestinal Epithelial Cells through Histone Acetylation

Abstract

Background: Butyrate, a fermentation product of intestinal bacteria, modifies chromatin structure through histone acetylation, thereby altering gene transcription. IL-8 and MCP-1 are chemokines, expressed by intestinal epithelial cells, which attract neutrophils and monocytes, respectively. We hypothesized that butyrate may alter 11-8 and MCP-1 expression by intestinal epithelial cells through histone acetylation. Materials and Methods: IL-8 and MCP-1 expression was measured by ELISA and RNA transfer blots. Acetylated histones were separated on acetic acid-urea-triton gels. Butyrate was compared to Trichostatin-A, a specific inhibitor of histone deacetylase and to other short chain fatty acids. Results: Caco-2 cells constitutively secreted MCP-1 but not IL-8. Butyrate reversibly decreased MCP-1 secretion. In contrast, butyrate increased IL-8 production. The effects of butyrate and Trichostatin-A were greater when cells were stimulated with IL-1(3. Butyrate and Trichostatin-A both increased histone acetylation. Trichostatin-A and other short chain fatty acids altered chemokine secretion according to their effect on histone acetylation. Conclusions: Butyrate reversibly switches chemokine secretion by epithelial cells through histone acetylation. We speculate that butyrate carries information from resident bacteria to epithelial cells. Epithelial cells transduce this signal through histone acetylation, modulating the secretion of chemokines.

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

“…These results indicate that the up-regulation of IL-8 by butyrate alone may involve an NF-kB-independent mechanism. This has been previously reported by Fusunyan et al, who showed that butyrate increased the production of IL-8 through histone acetylation [12]. Butyrate selectively induced histone acetylation at the Nod2 promoter but not at Nod1 or Tlr2.…”

“…2009. 39: 3529-3537 Chung-Hang Leung et al Butyrate enhances IL-8 secretion mediated by IL-1b, bacteria, and yeast, whereas it inhibits NF-kB activation by TNF-a and phorbol ester [12][13][14][15][33][34][35][36]. Among its diverse activities, the suppression of NF-kB activity through HDAC inhibition is the most frequently studied anti-inflammatory effect of butyrate [35,36].…”

“…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 that butyrate could be essential for the regulation of chemokine production mediated by bacterial substances in the intestine.…”

Butyrate Regulates the Expression of Pathogen-Triggered IL-8 in Intestinal Epithelia

“…Different studies reported that butyrate could both up-and down-regulate production of IL-8 (2-6). The up-regulatory effect may result from its chromatin remodeling action by inhibiting histone deacetylase (2). However, no satisfactory model is available to interpret its down-regulation of IL-8 expression.…”

Cytokine Responses of Intestinal Epithelial-Like Caco-2 Cells to Non-Pathogenic and Opportunistic Pathogenic Yeasts in the Presence of Butyric Acid

“…7,8) The exposure of IEC lines, including Caco-2, to butyric acid, a short chain fatty acid produced by bacterial carbohydrate fermentation in the mammalian intestine, 9,10) has been found to alter the cytokine secretion, NF-B activation, arachidonic cascade, cell cycles, cell differentiation and alkaline phosphatase activity of these cells. [11][12][13][14][15][16] We have previously shown that IEC-like Caco-2 cells cultured in a medium containing 10 mM butyric acid secreted interleukin-8 (IL-8/CXCL-8) in response to both non-pathogenic S. cerevisiae and the opportunistic pathogenic C. albicans.…”