Activation of mitogen‐activated protein kinase is involved in sphingosine 1‐phosphate‐stimulated interleukin‐6 synthesis in osteoblasts

FEBS Letters

Kozawa, Osamu¹  Matsuno, Hiroyuki¹  Uematsu, Toshihiko¹  Tokuda, Haruhiko² 

[1] Department of Pharmacology, Gifu University School of Medicine, Gifu 500, Obu, Aichi 474, Japan;Department of Internal Medicine, Chubu National Hospital, National Institute for Longevity Sciences, Obu, Aichi 474, Japan

关键词: Mitogen-activated protein kinase;    Sphingosine 1-phosphate;    Interleukin-6;    SPP;    sphingosine 1-phosphate;    TNF;    tumor necrosis factor-α;    IL-6;    interleukin-6;    MAP kinase;    mitogen-activated protein kinase;    α-MEM;    α-minimum essential medium;    FCS;    fetal calf serum;    MEK;    MAP kinase kinase;   

DOI  :  10.1016/S0014-5793(97)01366-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We previously showed that sphingosine 1-phosphate (SPP) acts as a second messenger for tumor necrosis factor α-induced interleukin-6 (IL-6) synthesis in osteoblast-like MC3T3-E1 cells. In the present study, we further investigated the mechanism of IL-6 synthesis induced by SPP in MC3T3-E1 cells. SPP significantly induced p42/p44 mitogen-activated protein (MAP) kinase activity. PD98059, an inhibitor of MAP kinase kinase, suppressed SPP-induced IL-6 synthesis as well as SPP-induced MAP kinase activation. The patterns of both inhibitions were similar. TMB-8, an inhibitor of Ca²⁺ mobilization from intracellular Ca²⁺ stores, significantly suppressed the SPP-induced IL-6 synthesis. These results strongly suggest that SPP-induced IL-6 synthesis is mediated via p42/p44 MAP kinase activation in osteoblast-like cells and that the SPP-induced IL-6 synthesis is dependent on intracellular Ca²⁺ mobilization.

【 授权许可】

Unknown