Fos proteins suppress dextran sulfate sodium-induced colitis through inhibition of NF-κB

Yasunari Takada, Neelanjan Ray, Eiji Ikeda, Tomohiro Kawaguchi, Masayoshi Kuwahara, Erwin F. Wagner, Koichi Matsuo

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The Fos family proteins, c-Fos and Fra-1, are components of the dimeric transcription factor AP-1, which is typically composed of Fos and Jun family proteins. We have previously shown that mice lacking c-Fos (Fos-/- mice) respond more strongly to LPS injection than do wild-type (wt) controls.We then examined the sensitivity of Fos-/- mice to acute inflammatory stress in a dextran sulfate sodium (DSS)-induced colitis model. We found that Fos -/- mice exhibited more severe weight loss, bleeding, diarrhea, and colon shortening than did wt mice, in association with higher TNF-α production and NF-κB activity in colon segments of DSS-treated Fos -/- mice. Furthermore, NF-κB inhibition suppressed severe DSS-induced colitis in Fos-/- mice. In contrast, Fra-1 transgenic (Tg) mice responded poorly to LPS injection, and Fra-1-overexpressing macrophages and fibroblasts showed reduced production of proinflammatory cytokines, NO, and NF-κB activity. Remarkably, in the DSS-induced colitis model, Fra-1 Tg mice showed less severe clinical scores of colitis than did wt mice. Consistently, proinflammatory cytokine production and NF-κB activity in colon segments of DSS-treated Fra-1 Tg mice were lower than in wt controls. These findings reveal that the absence of c-Fos and overexpression of Fra-1 respectively enhance and suppress the activation of NF-κB in DSS-induced inflammatory stress. In this paper, we propose that AP-1 transcription factors containing c-Fos or Fra-1 are negative regulators of NF-κB-mediated stress responses.

Original languageEnglish
Pages (from-to)1014-1021
Number of pages8
JournalJournal of Immunology
Volume184
Issue number2
DOIs
Publication statusPublished - 2010 Jan 15

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Dextran Sulfate
Colitis
Proteins
Transgenic Mice
Colon
Transcription Factor AP-1
Cytokines
Proto-Oncogene Proteins c-fos
Injections
Weight Loss
Diarrhea
Fibroblasts
Macrophages
Hemorrhage

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Fos proteins suppress dextran sulfate sodium-induced colitis through inhibition of NF-κB. / Takada, Yasunari; Ray, Neelanjan; Ikeda, Eiji; Kawaguchi, Tomohiro; Kuwahara, Masayoshi; Wagner, Erwin F.; Matsuo, Koichi.

In: Journal of Immunology, Vol. 184, No. 2, 15.01.2010, p. 1014-1021.

Research output: Contribution to journalArticle

Takada, Y, Ray, N, Ikeda, E, Kawaguchi, T, Kuwahara, M, Wagner, EF & Matsuo, K 2010, 'Fos proteins suppress dextran sulfate sodium-induced colitis through inhibition of NF-κB', Journal of Immunology, vol. 184, no. 2, pp. 1014-1021. https://doi.org/10.4049/jimmunol.0901196
Takada Y, Ray N, Ikeda E, Kawaguchi T, Kuwahara M, Wagner EF et al. Fos proteins suppress dextran sulfate sodium-induced colitis through inhibition of NF-κB. Journal of Immunology. 2010 Jan 15;184(2):1014-1021. https://doi.org/10.4049/jimmunol.0901196
Takada, Yasunari ; Ray, Neelanjan ; Ikeda, Eiji ; Kawaguchi, Tomohiro ; Kuwahara, Masayoshi ; Wagner, Erwin F. ; Matsuo, Koichi. / Fos proteins suppress dextran sulfate sodium-induced colitis through inhibition of NF-κB. In: Journal of Immunology. 2010 ; Vol. 184, No. 2. pp. 1014-1021.
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