Prostaglandin F2α upregulates interleukin-6 production in human gingival fibroblasts

Prostaglandin F-2 alpha (PGF(2 alpha)) is a bioactive lipid mediator which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF(2 alpha) in periodontal lesions are poorly understood. In the present study, we investigated the effect of PGF(2 alpha) on interleukin (IL)-6 production in human gingival fibroblasts (HGF), PGF(2 alpha) stimulated IL-6 production in a time- and concentration-dependent fashion. IL-1 beta and turner necrosis factor alpha. (TNF alpha). proinflammatory cytokines, induced IL-6 production in a time-dependent manner, and PGF(2 alpha) synergistically enhanced IL-6 production induced by IL-1 beta and TNF alpha. IL-6 mRNA was expressed in PGF(2 alpha)-stilnulated HGF, and PGF(2 alpha) increased IL-6 mRNA levels induced by IL-1 beta and TNF alpha. Fluprostenol, a selective FP receptor agonist, could mimic PGF(2 alpha)-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(2 alpha) was investigated using TMB-8, an inhibitor of Ca2+ mobilization from intracellular stores, and calphostin C, an inhibitor of PKC. TMB-8 significantly suppressed PGF(2 alpha)-induced IL-6 production. whereas calphostin C showed a stimulatory effect on PGF(2 alpha)-induced IL-6 production. From these data, we suggest that PGF(2 alpha) upregulates IL-6 production through FP receptors in HGF, that PGF(2 alpha) synergistically enhances IL-6 production in IL-1 beta- and INF alpha -stimulated HGF. and that PGF(2 alpha)-indnced IL-6 production may be dependent on intracellular Ca2+ mobilization and be downregulated by PKC activation. PGF(2 alpha) may be involved in the pathogenesis of periodontal disease by enhancing IL-6 levels in periodontal lesions.