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IL-10 attenuates IFN-alpha-activated STAT1 in the liver: involvement of SOCS2 and SOCS3

X Shen1, F Hong, V A Nguyen

  • 1Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.

FEBS Letters
|October 18, 2000
PubMed

Interleukin-10 (IL-10) has been used in the treatment of viral hepatitis in interferon-alpha (IFN-alpha) non-responders while patients who have high levels of IL-10 are poorly responsive to IFN-alpha. The mechanism underlying such controversial functions of IL-10 remains unknown. Here we demonstrated that injection of IL-10 into mice attenuated IFN-alpha-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-alpha-induced reporter activity in hepatic cells. These findings suggest that IL-10 inhibits IFN-alpha-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-alpha therapy in patients who have high levels of IL-10 and recommends that IL-10 treatment for viral hepatitis should be cautious.

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