title: Prostaglandin F2alpha upregulates interleukin-6 production in human gingival fibroblasts.
abstract: 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.
authors.affiliation: Department of Periodontology, Faculty of Dentistry, Tokyo Medical & Dental University, Japan. kazuyuki-noguchi.peri@dent.tmd.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Noguchi
authors.forename: H
authors.initials: H
authors.lastname: Endo
authors.forename: H
authors.initials: H
authors.lastname: Kondo
authors.forename: I
authors.initials: I
authors.lastname: Ishikawa
mesh_terms: D002118:Calcium / Q000037:antagonists & inhibitors; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004357:Drug Synergism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D009281:Naphthalenes / Q000494:pharmacology; D010510:Periodontal Diseases / Q000209:etiology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis; D011982:Receptors, Prostaglandin / Q000819:agonists; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D000093242:Interleukin-6 Inhibitors
chemical_list: D002118:Calcium; D002121:Calcium Channel Blockers; D015237:Dinoprost; D004791:Enzyme Inhibitors; D005707:Gallic Acid; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D009281:Naphthalenes; D011461:Prostaglandins F, Synthetic; D011493:Protein Kinase C; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C006326:fluprostenol; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; C058819:calphostin C