Acetate inhibits NFAT activation in T cells via importin β1 interference

Kazuhiro Ishiguro, Takafumi Ando, Osamu Maeda, Naoki Ohmiya, Yasumasa Niwa, Hidemi Goto

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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-κB activation. Moreover, acetate impaired the nuclear translocation of NFAT but not that of NF-κB. Unlike cyclosporin A (CsA), acetate did not affect the dephosphorylation of NFAT and calcineurin activity. Acetate impaired the binding of NFAT to importin β1, which is involved in NFAT nuclear translocation. NFAT 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 β1 in T cells and that acetate can potentially act as an anti-inflammatory agent.

Original languageEnglish
Pages (from-to)2309-2316
Number of pages8
JournalEuropean Journal of Immunology
Volume37
Issue number8
DOIs
Publication statusPublished - 01-08-2007

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Karyopherins
Acetates
T-Lymphocytes
Cyclosporine
Trinitrobenzenesulfonic Acid
Dinitrofluorobenzene
Volatile Fatty Acids
Calcineurin
Dermatitis
Colitis
Dexamethasone
Fermentation
Colon
Anti-Inflammatory Agents
Transcription Factors
Alcohols

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ishiguro, Kazuhiro ; Ando, Takafumi ; Maeda, Osamu ; Ohmiya, Naoki ; Niwa, Yasumasa ; Goto, Hidemi. / Acetate inhibits NFAT activation in T cells via importin β1 interference. In: European Journal of Immunology. 2007 ; Vol. 37, No. 8. pp. 2309-2316.
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Acetate inhibits NFAT activation in T cells via importin β1 interference. / Ishiguro, Kazuhiro; Ando, Takafumi; Maeda, Osamu; Ohmiya, Naoki; Niwa, Yasumasa; Goto, Hidemi.

In: European Journal of Immunology, Vol. 37, No. 8, 01.08.2007, p. 2309-2316.

Research output: Contribution to journalArticle

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