Effect of vitamin D3 on interleukin-6 synthesis induced by prostaglandins in osteoblasts.

In previous studies, we have shown that prostaglandin F2alpha (PGF2alpha) stimulates interleukin-6 (IL-6) synthesis via activation of protein kinase C in osteoblast-like MC3T3-E1 cells, and that prostaglandin E1 (PGE1) induces the synthesis of IL-6 through protein kinase A activation. In the present study, we investigated the effect of vitamin D3 on IL-6 synthesis in MC3T3-E1 cells. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), an active form of vitamin D3, inhibited the IL-6 synthesis induced by PGF2alpha or PGE1. On the contrary, 24,25-dihydroxyvitamin D3, an inactive form of vitamin D3, had no effect. 1,25-(OH)2D3 did not affect the IL-6 synthesis stimulated by 12-O-tetradecanoyl-phorbol-13-acetate, an activator of protein kinase C. The IL-6 synthesis induced by cholera toxin or forskolin was significantly inhibited by 1,25-(OH)2D3. However, 1,25-(OH)2D3 had little effect on the IL-6 synthesis induced by dibutyryl cAMP. These results strongly suggest that 1,25-(OH)2D3, an active form of vitamin D3, inhibits IL-6 synthesis at both the protein kinase C pathway and the protein kinase A pathway in osteoblasts.