title: Interleukin (IL)-17 enhances prostaglandin F(2 alpha)-stimulated IL-6 synthesis in osteoblasts.
abstract: We previously showed that prostaglandin F(2alpha) (PGF(2alpha)) and endothelin-1 (ET-1) induce interleukin (IL)-6 through the activation of protein kinase C-dependent p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. It has recently been reported that tumor necrosis factor-alpha-induced IL-6 synthesis is amplified by IL-17 in these cells. In the present study, we investigated the effect of IL-17 on the IL-6 synthesis stimulated by PGF(2alpha) in MC3T3-E1 cells. IL-17 significantly enhanced the PGF(2alpha)-induced IL-6 synthesis in a dose-dependent manner in the range between 0.1 and 10 ng/ml. IL-17 also enhanced the IL-6 synthesis stimulated by 12- O -tetradecanoylphorbol-13-acetate, a direct activator of protein kinase C. In addition, IL-17 amplified the IL-6 synthesis induced by ET-1. However, IL-17 hardly affected the phosphorylation of p44/p42 MAP kinase induced by PGF(2alpha) or ET-1. These results strongly suggest that IL-17 enhances the IL-6 synthesis stimulated by PGF(2alpha) as well as ET-1 in osteoblasts, and that the effect is exerted at a point downstream from p44/p42 MAP kinase.
authors.affiliation: Department of Internal Medicine, Chubu National Hospital, National Institute for Longevity Sciences, Obu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tokuda
authors.forename: O
authors.initials: O
authors.lastname: Kozawa
authors.forename: T
authors.initials: T
authors.lastname: Uematsu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003627:Data Interpretation, Statistical; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D020381:Interleukin-17 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D020381:Interleukin-17; D015850:Interleukin-6; D015237:Dinoprost; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate