Noguchi K, Endo H, Kondo H, Ishikawa I
Department of Periodontology, Faculty of Dentistry, Tokyo Medical & Dental University, Japan.
J Periodontal Res. 2001 Apr;36(2):80-7. doi: 10.1034/j.1600-0765.2001.360203.x.
Prostaglandin F2alpha (PGF2alpha) is a bioactive lipid mediator which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2alpha in periodontal lesions are poorly understood. In the present study, we investigated the effect of PGF2alpha on interleukin (IL)-6 production in human gingival fibroblasts (HGF). PGF2alpha stimulated IL-6 production in a time- and concentration-dependent fashion. IL-1beta and tumor necrosis factor alpha (TNFalpha), proinflammatory cytokines, induced IL-6 production in a time-dependent manner, and PGF2alpha synergistically enhanced IL-6 production induced by IL-1beta and TNFalpha. IL-6 mRNA was expressed in PGF2alpha-stimulated HGF, and PGF2alpha increased IL-6 mRNA levels induced by IL-1beta and TNFalpha. Fluprostenol, a selective FP receptor agonist, could mimic PGF2alpha-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 PGF2alpha was investigated using TMB-8, an inhibitor of Ca2+ mobilization from intracellular stores, and calphostin C, an inhibitor of PKC. TMB-8 significantly suppressed PGF2alpha-induced IL-6 production, whereas calphostin C showed a stimulatory effect on PGF2alpha-induced IL-6 production. From these data, we suggest that PGF2alpha upregulates IL-6 production through FP receptors in HGF, that PGF2alpha synergistically enhances IL-6 production in IL-1beta- and TNFalpha-stimulated HGF, and that PGF2alpha-induced IL-6 production may be dependent on intracellular Ca2+ mobilization and be downregulated by PKC activation. PGF2alpha may be involved in the pathogenesis of periodontal disease by enhancing IL-6 levels in periodontal lesions.
前列腺素F2α（PGF2α）是一种生物活性脂质介质，有人认为它参与了牙周疾病的发病机制。然而，PGF2α在牙周病变中的作用尚不清楚。在本研究中，我们研究了PGF2α对人牙龈成纤维细胞（HGF）中白细胞介素（IL）-6产生的影响。PGF2α以时间和浓度依赖性方式刺激IL-6的产生。促炎细胞因子IL-1β和肿瘤坏死因子α（TNFα）以时间依赖性方式诱导IL-6的产生，并且PGF2α协同增强IL-1β和TNFα诱导的IL-6产生。IL-6 mRNA在PGF2α刺激的HGF中表达，并且PGF2α增加了IL-1β和TNFα诱导的IL-6 mRNA水平。氟前列醇，一种选择性FP受体激动剂，可以模拟PGF2α诱导的IL-6产生。由于FP受体与细胞内钙升高和蛋白激酶C（PKC）激活相关，因此使用TMB-8（一种细胞内钙库动员抑制剂）和钙泊三醇（一种PKC抑制剂）研究了PGF2α诱导IL-6产生的机制。TMB-8显著抑制PGF2α诱导的IL-6产生，而钙泊三醇对PGF2α诱导的IL-6产生显示出刺激作用。从这些数据中，我们认为PGF2α通过HGF中的FP受体上调IL-6产生，PGF2α在IL-1β和TNFα刺激的HGF中协同增强IL-6产生，并且PGF2α诱导的IL-6产生可能依赖于细胞内钙动员并被PKC激活下调。PGF2α可能通过提高牙周病变中的IL-6水平参与牙周疾病的发病机制。
