Cyclic Adenosine Monophosphate Suppresses the Transcription of Proinflammatory Cytokines via the Phosphorylated c-Fos Protein

Keiko Koga, Giichi Takaesu, Ryoko Yoshida, Mako Nakaya, Takashi Kobayashi, Ichiko Kinjyo, Akihiko Yoshimura

研究成果: Article査読

105 被引用数 (Scopus)

抄録

Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production from monocytic cells. Enhanced expression of interleukin-10 (IL-10) has been suggested to be the mechanism of suppression. However, cAMP is still capable of suppressing production of the cytokines TNF-α and IL-12 in IL-10-deficient dendritic cells (DCs). Here, we demonstrated that the transcription factor c-Fos was responsible for the cAMP-mediated suppression of inflammatory cytokine production. c-Fos accumulated at high amounts in response to cAMP and lipopolysaccharide (LPS). Overexpression of c-Fos suppressed LPS-induced cytokine production, whereas cAMP-mediated suppression of TNF-α and IL-12 was impaired in Fos-/- DCs or in RAW264.7 cells treated with c-Fos siRNA. c-Fos physically interacted with p65 protein and reduced the recruitment of p65 to the Tnf promoter. Multiple sites of c-Fos were phosphorylated by the IKKβ protein. Thus, we propose that c-Fos is a substrate of IKKβ and is responsible for the immunosuppressive effect of cAMP.

本文言語English
ページ(範囲)372-383
ページ数12
ジャーナルImmunity
30
3
DOI
出版ステータスPublished - 2009 3 20

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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