Extracellular sphingomyelinase induces interleukin-6 synthesis in osteoblasts

✍ Scribed by Haruhiko Tokuda; Osamu Kozawa; Atsushi Harada; Toshihiko Uematsu

• Book ID: 101259727
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 80 KB
• Volume: 72
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19990201)72:2<262::aid-jcb10>3.0.co;2-n

✦ Synopsis

In osteoblast-like MC3T3-E1 cells, we have recently reported that sphingosine 1-phosphate among sphingomyelin metabolites acts as a second messenger for tumor necrosis factor-alpha (TNF)-induced interleukin-6 (IL-6) synthesis. In the present study, we investigated the effect of extracellular sphingomyelinase on IL-6 synthesis in MC3T3-E1 cells. Sphingomyelinase stimulated IL-6 synthesis in a time-dependent manner for up to 24 h. This stimulative effect was dose dependent in the range between 1 and 300 mU/ml. Calphostin C, a highly and potent inhibitor of protein kinase C, enhanced sphingomyelinase-induced IL-6 synthesis. DL-Threo-dihydrosphingosine, an inhibitor of sphingosine kinase, significantly inhibited the IL-6 synthesis induced by sphingomyelinase. Sphingomyelinase markedly elicited sphingomyelin hydrolysis. In addition, the effect of a combination of sphingomyelinase and TNF on IL-6 synthesis was synergistic. These results strongly suggest that extracellular sphingomyelinase induces sphingomyelin hydrolysis in osteoblasts, resulting in IL-6 synthesis, and that protein kinase C acts as a negative controller of the IL-6 synthesis.