Inhibitory effects of the JAK inhibitor CP690,550 on human CD4+ T lymphocyte cytokine production

BMC Immunology

Hiromi Ishibashi¹  Minoru Nakamura¹  Atsushi Kawakami²  Satoshi Yamasaki²  Yoshihiro Aiba¹  Yuka Jiuchi¹  Yumi Maeda¹  Atsumasa Komori¹  Tomohiro Koga¹  Yasumori Izumi¹  Taiichiro Miyashita¹  Kiyoshi Migita¹ 

[1]Department of Rheumatology and Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura 856-8652, Japan

[2]Department of Rheumatology, Nagasaki University Hospital, Sakamoto 1-7-1 Nagasaki 852-8501, Japan

关键词: T lymphocytes;    signal transducers and activators of transcription;    Janus kinase;    cytokines;    550;    CP690;   

Others  :  1077985
DOI  :  10.1186/1471-2172-12-51

 received in 2011-01-21, accepted in 2011-08-31,  发布年份 2011

【 摘 要 】

Background

The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis. The present study was undertaken to assess the effects of CP690,550 on cytokine production and cellular signaling in human CD4⁺ T cells.

Results

CD4⁺ T cells produced IL-2, IL-4, IL-17, IL-22 and IFN-γ in following stimulation with a CD3 antibody. At the optimal concentration, CP690,550 almost completely inhibited the production of IL-4, IL-17, IL-22 and IFN-γ from these activated CD4⁺ T cells, but only had marginal effects on IL-2 production. Moreover CP690,550 inhibited anti-CD3-induced phosphorylation of STAT1, STAT3, STAT4, STAT5, and STAT6, but not the TCR-associated phosphorylation of ZAP-70.

Conclusions

Therefore, CP690,550-mediated modification of the JAK/STAT pathway may be a new immunosuppressive strategy in the treatment of autoimmune diseases.

【 授权许可】

   
2011 Migita et al; licensee BioMed Central Ltd.

【 图 表 】

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