Prostaglandin F2α, (PGF2α) is a bioactive lipid mediator which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2α in periodontal lesions are poorly understood. In the present study, we investigated the effect of PGF2α, on interleukin (IL)-6 production in human gingival fibroblasts (HGF). PGF2α 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 PGF2α, synergistically enhanced IL-6 production induced by IL-1β and TNFα. IL-6 mRNA was expressed in PGF2α-stimulated HGF, and PGF2α, increased IL-6 mRNA levels induced by IL-1β and TNFα. Fluprostenol, a selective FP receptor agonist, could mimic PGF2α-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 PGF2α was investigated using TMB-8. an inhibitor of Ca2+ mobilization from intracellular stores, and calphostin C. an inhibitor of PKC. TMB-8 significantly suppressed PGF2α-induced IL-6 production, whereas calphostin C showed a stimulatory effect on PGF2α,-induced IL-6 production. From these data, we suggest that PGF2α upregulates IL-6 production through FP receptors in HGF, that PGF2α, synergistically enhances IL-6 production in IL-1β- and TNFα-stimulated HGF, and that PGF2α,-induced IL-6 production may be dependent on intracellular Ca2+ mobilization and be downregulated by PKC activation. PGF2α, may be involved in the pathogenesis of periodontal disease by enhancing IL-6 levels in periodontal lesions.
CITATION STYLE
Noguchi, K., Endo, H., Kondo, H., & Ishikawa, I. (2001). Prostaglandin F2α upregulates interleukin-6 production in human gingival fibroblasts. Journal of Periodontal Research, 36(2), 80–87. https://doi.org/10.1034/j.1600-0765.2001.360203.x
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