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Cyclic Adenosine Monophosphate Suppresses the Transcription of Proinflammatory Cytokines via the Phosphorylated c-Fos Protein
被引:119
作者:
Koga, Keiko
[1
]
Takaesu, Giichi
[1
]
Yoshida, Ryoko
[1
,2
]
Nakaya, Mako
[1
]
Kobayashi, Takashi
[1
]
Kinjyo, Ichiko
[2
]
Yoshimura, Akihiko
[1
,2
,3
]
机构:
[1] Kyushu Univ, Div Mol & Cellular Immunol, Med Inst Bioregulat, Higashi Ku, Fukuoka 8128582, Japan
[2] Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo 1608582, Japan
[3] Japan Sci & Technol Agcy, CREST, Chiyoda Ku, Tokyo 1020075, Japan
来源:
关键词:
IMMUNE-RESPONSES;
B P65;
KINASE;
ACTIVATION;
BINDING;
DEGRADATION;
MACROPHAGES;
FAMILY;
CELLS;
GENE;
D O I:
10.1016/j.immuni.2008.12.021
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
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; TINIF-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 (LIPS). 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 IKK beta protein. Thus, we propose that c-Fos is a substrate of IKK beta and is responsible for the immunosuppressive effect of cAMP.
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页码:372 / 383
页数:12
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