ScholarWorks@숙명여자대학교

초록

Interleukin (IL)-32 has been associated with a variety of inflammatory diseases including rheumatoid arthritis, vasculitis and Crohn's disease. We have previously reported that IL-32 gamma, the IL-32 isoform with the highest biological activity, could act as an immune modulator through regulation of dendritic cell (DC) functions in immune responses. Cell locomotion is crucial for induction of an effective immune response. In this study, we investigated the effect and underlying mechanisms of IL-32 gamma on recruitment of T cells. IL-32 gamma upregulated the expression of several chemokines including CCL2, CCL4, and CCL5 in the DCs. In particular, IL-32 gamma significantly increased CCL5 expression in a dose-dependent manner. Treatment with JNK and NF-kappa B inhibitors suppressed IL-32 gamma-induced CCL5 expression in DCs, indicating that IL-32 gamma induced CCL5 production through the JNK and NF-kappa B pathways. Furthermore, supernatants from IL-32 gamma-treated DCs showed chemotactic activities controlling migration of activated CD4(+) and CD8(+) T cells, and these activities were suppressed by addition of neutralizing anti-CCL5 antibody. These results show that IL-32 gamma effectively promotes migration of activated T cells via CCL5 production in DCs. The chemotactic potential of IL-32 gamma may explain the pro-inflammatory effects of IL-32 and the pathologic role of IL-32 in immune disorders such as rheumatoid arthritis. (C) 2014 Elsevier Inc. All rights reserved.

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