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Prostaglandin F 2α upregulates interleukin‐6 production in human gingival fibroblasts
Author(s) -
Noguchi Kazuyuki,
Endo Hirahito,
Kondo Hirofumi,
Ishikawa Isao
Publication year - 2001
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1034/j.1600-0765.2001.360203.x
Subject(s) - calphostin c , endocrinology , calphostin , medicine , proinflammatory cytokine , chemistry , receptor , tumor necrosis factor alpha , prostaglandin e , intracellular , prostaglandin , interleukin , cytokine , calcium in biology , protein kinase c , signal transduction , biology , inflammation , biochemistry
Prostaglandin F 2α (PGF 2α ) is a bioactive lipid mediator which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF 2α in periodontal lesions are poorly understood. In the present study, we investigated the effect of PGF 2α on interleukin (IL)‐6 production in human gingival fibroblasts (HGF). PGF 2α stimulated IL‐6 production in a time‐ and concentration‐dependent fashion. IL‐1β and tumor necrosis factor α(TNFα), proinflammatory cytokines, induced IL‐6 production in a time‐dependent manner, and PGF 2α synergistically enhanced IL‐6 production induced by IL‐1β and TNFα. IL‐6 mRNA was expressed in PGF 2α ‐stimulated HGF, and PGF 2α increased IL‐6 mRNA levels induced by IL‐1β and TNFα. Fluprostenol, a selective FP receptor agonist, could mimic PGF 2α ‐induced IL‐6 production. Since FP receptors are coupled to elevation of intracellular calcium and activation of protein kinase C (PKC), the mechanism of IL‐6 production by PGF 2α was investigated using TMB‐8, an inhibitor of Ca 2+ mobilization from intracellular stores, and calphostin C, an inhibitor of PKC. TMB‐8 significantly suppressed PGF 2α ‐induced IL‐6 production, whereas calphostin C showed a stimulatory effect on PGF 2α ‐induced IL‐6 production. From these data, we suggest that PGF 2α upregulates IL‐6 production through FP receptors in HGF, that PGF 2α synergistically enhances IL‐6 production in IL‐1β‐ and TNFα‐stimulated HGF, and that PGF 2α ‐induced IL‐6 production may be dependent on intracellular Ca 2+ mobilization and be downregulated by PKC activation. PGF 2α may be involved in the pathogenesis of periodontal disease by enhancing IL‐6 levels in periodontal lesions.