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Activation of mitogen‐activated protein kinase is involved in sphingosine 1‐phosphate‐stimulated interleukin‐6 synthesis in osteoblasts
Author(s) -
Kozawa Osamu,
Tokuda Haruhiko,
Matsuno Hiroyuki,
Uematsu Toshihiko
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01366-5
Subject(s) - sphingosine 1 phosphate , sphingosine , microbiology and biotechnology , mitogen activated protein kinase , sphingosine kinase , kinase , map kinase kinase kinase , mitogen activated protein kinase kinase , protein kinase a , ask1 , sphingosine kinase 1 , chemistry , osteoblast , biology , biochemistry , in vitro , receptor
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 Ca 2+ mobilization from intracellular Ca 2+ 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 Ca 2+ mobilization.