Acetate inhibits NFAT activation in T cells via importin β1 interference

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

研究成果: Article

16 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)2309-2316
ページ数8
ジャーナルEuropean Journal of Immunology
37
発行部数8
DOI
出版物ステータスPublished - 01-08-2007
外部発表Yes

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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

これを引用

Ishiguro, Kazuhiro ; Ando, Takafumi ; Maeda, Osamu ; Ohmiya, Naoki ; Niwa, Yasumasa ; Goto, Hidemi. / Acetate inhibits NFAT activation in T cells via importin β1 interference. :: European Journal of Immunology. 2007 ; 巻 37, 番号 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.

:: European Journal of Immunology, 巻 37, 番号 8, 01.08.2007, p. 2309-2316.

研究成果: Article

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