1. ¹Laboratory of Immunology, Department of Biological Science, Institute for Basic Science, Sungkyunkwan University, Suwon, Korea
2. ²Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Science, Yonsei University School of Medicine, Seoul, Korea

Correspondence: Dr C-E Lee, Laboratory of Immunology, Department of Biological Science, Sungkyunkwan University, 300 Cheon-Cheon Dong, Suwon 440-746, Korea. E-mail: celee@skku.edu

Received 17 February 2009; Revised 17 April 2009; Accepted 5 May 2009; Published online 29 June 2009.

Abstract

Suppressors of cytokine signaling (SOCS) are negative regulators of cytokine-induced signal transduction, which play multiple roles in cell growth, differentiation and apoptosis. In this study, the regulatory role of SOCS in oxidative stress-induced apoptosis was investigated. In Jurkat T cells and mouse splenocytes, we have found that SOCS1 is induced in response to tumor necrosis factor- or H₂O₂, concomitant with the activation of Jaks which act as important mediators of reactive oxygen species (ROS)-induced apoptosis upstream of p38 mitogen-activated protein kinase. Using SOCS1 overexpressing or knockdown Jurkat T-cell systems we clearly demonstrate that, SOCS1 inhibits the ROS-mediated apoptosis. The antiapoptotic action of SOCS1 was exerted not only by suppressing Jaks, but also by sustaining protein tyrosine phosphatase (PTP) activities. Notably, SOCS1-transduced cells displayed increase in thioredoxin levels and decrease in ROS generation induced by oxidative stress. In addition, the Jak-inhibiting and PTP-sustaining effect of SOCS1 was significantly reduced on thioredoxin ablation. Moreover, coimmunoprecipitation data revealed molecular interaction of SHP1 or CD45 with thioredoxin, which was promoted in SOCS1-transfected cells. Together, our data strongly suggest that both the protection of PTPs by thioredoxin from ROS attack and the attenuation of Jaks account for the antiapoptotic function of SOCS1 in immune cells under oxidative stress.