期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 37, 期 8, 页码 2309-2316出版社
WILEY
DOI: 10.1002/eji.200737180
关键词
acetates; importins; T lymphocytes; transcription factors
类别
Acetate is a principal short chain fatty acid produced by bacterial fermentation in the colon and a major end product of alcohol metabolism. In the present study, we assessed the effects of acetate on T cell activation and found that acetate inhibited NFAT activation but not NF-kappa B activation. Moreover, acetate impaired the nuclear translocation of NFAT but not that of NF-kappa B. Unlike cyclosporin A (CsA), acetate did not affect the dephosphorylation of NFAT and calcineurin activity. Acetate impaired the binding of NFAT to importin beta 1, which is involved in NFAT nuclear translocation. NEAT is a critical transcription factor in cytokine and early response gene expression in activated T cells. Agents targeting NFAT such as CsA are used to suppress harmful immune responses in inflammatory diseases. Therefore, we also evaluated the efficacy of acetate in murine models of inflammatory diseases, and found that acetate administration (as well as administration of dexamethasone) attenuated trinitrobenzenesulfonic acid-induced colitis and dinitrofluorobenzene-induced dermatitis. These findings indicate for the first time that acetate inhibits NFAT activation by interfering with the interaction between NFAT and importin beta 1 in T cells and that acetate can potentially act as an anti-inflammatory agent.
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