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

Abstract In previous studies, we have shown that prostaglandin F 2α (PGF 2α ) stimulates interleukin-6 (IL-6) synthesis via activation of protein kinase C in osteoblast-like MC3T3-E1 cells, and that prostaglandin E 1 (PGE 1 ) induces the synthesis of IL-6 through protein kinase A activation. In the present study, we investigated the effect of vitamin D 3 on IL-6 synthesis in MC3T3-E1 cells. 1,25-Dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ), an active form of vitamin D 3 , inhibited the IL-6 synthesis induced by PGF 2α or PGE 1 . On the contrary, 24,25-dihydroxyvitamin D 3 , an inactive form of vitamin D 3 , had no effect. 1,25-(OH) 2 D 3 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) 2 D 3 . However, 1,25-(OH) 2 D 3 had little effect on the IL-6 synthesis induced by dibutyryl cAMP. These results strongly suggest that 1,25-(OH) 2 D 3 , an active form of vitamin D 3 , inhibits IL-6 synthesis at both the protein kinase C pathway and the protein kinase A pathway in osteoblasts.