Your browser doesn't support javascript.

Biblioteca Virtual em Saúde


Home > Pesquisa > ()
Imprimir Exportar

Formato de exportação:


Adicionar mais destinatários
| |

Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c-Fos protein.

Koga, Keiko; Takaesu, Giichi; Yoshida, Ryoko; Nakaya, Mako; Kobayashi, Takashi; Kinjyo, Ichiko; Yoshimura, Akihiko.
Immunity; 30(3): 372-83, 2009 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-19285436
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-alpha 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-alpha 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 IKKbeta protein. Thus, we propose that c-Fos is a substrate of IKKbeta and is responsible for the immunosuppressive effect of cAMP.
Selo DaSilva