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Suppressive action of acetate on interleukin‐8 production via tubulin‐α acetylation
Author(s) -
Ishiguro Kazuhiro,
Ando Takafumi,
Maeda Osamu,
Watanabe Osamu,
Goto Hidemi
Publication year - 2014
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2014.31
Subject(s) - acetylation , chemistry , microbiology and biotechnology , biology , biochemistry , gene
Acetate is the major short‐chain fatty acid produced by commensal bacteria in the gut and is known as a nutrient source for epithelial cells of the mucosa. Acetate also suppresses interleukin (IL)‐2 production in T cells by inhibiting nuclear factor of activated T cells (NFAT) nuclear translocation via tubulin‐α acetylation. Using acetylation of tubulin‐α as a biomarker, we have examined the influence of acetate in the large intestine. Because of high concentrations of acetate in fecal material, tubulin‐α acetylation is dominant in the proximal large intestine relative to other sections of the large intestine and is induced in epithelial cells of the colonic mucosa. Flagellin stimulation induces IL‐8 production in epithelial cells and acetate suppresses this IL‐8 production via tubulin‐α acetylation. Flagellin stimulation activates nuclear factor‐κB, CREB and AP‐1, but not NFAT. Of these transcription factors, acetate specifically inhibits AP‐1 activation. Acetate impairs flagellin‐induced activation of the Rap1‐MEK‐ERK‐Elk‐1 pathway with acetylation of tubulin‐α that is bound to Rap1, resulting in reduced expression of c‐Fos, a subunit of AP‐1. These findings reveal a novel action of acetate via tubulin‐α acetylation in epithelial cells of the colonic mucosa.