IL‐10 attenuates IFN‐α‐activated STAT1 in the liver: involvement of SOCS2 and SOCS3

FEBS Letters

Nguyen, Van-Anh¹  Gao, Bin¹  Hong, Feng¹  Shen, Xuening¹ 

[1] Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA 23298, USA

关键词: Interleukin 10;    Interferon;    Liver;    Signal transducer and activator transcription factor;    Suppressor of cytokine signal;    Viral hepatitis;    IL-10;    interleukin-10;    IFN;    interferon;    STAT;    signal transducer and activator transcription factor;    SOCS;    suppressor of cytokine signal;    RT-PCR;    Reverse transcriptase-polymerase chain reaction;   

DOI  :  10.1016/S0014-5793(00)01905-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Interleukin-10 (IL-10) has been used in the treatment of viral hepatitis in interferon-α (IFN-α) non-responders while patients who have high levels of IL-10 are poorly responsive to IFN-α. The mechanism underlying such controversial functions of IL-10 remains unknown. Here we demonstrated that injection of IL-10 into mice attenuated IFN-α-induced signal transducer and activator transcription factor (STAT)1 tyrosine phosphorylation in the liver. Reverse transcriptase-polymerase chain reaction assay demonstrated that mouse liver expressed high levels of IL-10 receptor 2 (IL-10R2) but low levels of IL-10R1. Injection of IL-10 into mice activated STAT3 but not STAT1 tyrosine phosphorylation and induced suppressor of cytokine signal 2 (SOCS2), SOCS3, and cytokine-inducible SH2 protein (CIS) mRNA expression in the liver. Furthermore, overexpression of SOCS2 or SOCS3 inhibited IFN-α-induced reporter activity in hepatic cells. These findings suggest that IL-10 inhibits IFN-α-activated STAT1 in the liver, at least in part, by inducing SOCS2, SOCS3, and CIS expression, which may be responsible for the resistance of IFN-α therapy in patients who have high levels of IL-10 and recommends that IL-10 treatment for viral hepatitis should be cautious.

【 授权许可】

Unknown