Interleukin (IL)-17 enhances tumor necrosis factor-α-stimulated IL-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts

✍ Scribed by Haruhiko Tokuda; Yosuke Kanno; Akira Ishisaki; Motoki Takenaka; Atsushi Harada; Osamu Kozawa

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 184 KB
• Volume: 91
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20004

✦ Synopsis

Abstract

Inflammatory cytokines are well known to play crucial roles in the pathogenesis of rheumatoid arthritis. Among them, interleukin (IL)‐17 is a cytokine that is mainly synthesized by activated T cells and its receptors are present in osteoblasts. The synthesis of IL‐6, known to stimulate osteoclastic bone resorption, is reportedly responded to bone resorptive agents such as tumor necrosis factor‐α (TNF‐α) in osteoblasts. It has been reported that IL‐17 enhances TNF‐α‐stimulated IL‐6 synthesis in osteoblast‐like MC3T3‐E1 cells. We previously showed that sphingosine 1‐phosphate (S1‐P) mediates TNF‐α‐stimulated IL‐6 synthesis in these cells. In the present study, we investigated the mechanism of IL‐17 underlying enhancement of IL‐6 synthesis in MC3T3‐E1 cells. IL‐17 induced phosphorylation of p38 mitogen‐activated protein (MAP) kinase. SB203580 and PD169316, specific inhibitors of p38 MAP kinase, significantly reduced the enhancement by IL‐17 of TNF‐α‐stimulated IL‐6 synthesis. IL‐17 also amplified S1‐P‐stimulated IL‐6 synthesis, and the amplification by IL‐17 was suppressed by SB203580. Anisomycin, an activator of p38 MAP kinase, which alone had no effect on IL‐6 level, enhanced the IL‐6 synthesis stimulated by TNF‐α. SB203580 and PD169316 inhibited the amplification by anisomycin of the TNF‐α‐induced IL‐6 synthesis. Taken together, our results strongly suggest that IL‐17 enhances TNF‐α‐stimulated IL‐6 synthesis via p38 MAP kinase activation in osteoblasts. © 2004 Wiley‐Liss, Inc.