title: Binary regulation of interleukin (IL)-6 production by EP1 and EP2/EP4 subtypes of PGE2 receptors in IL-1beta-stimulated human gingival fibroblasts.
abstract: Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors, which are divided into four subtypes of EP1, EP2, EP3 and EP4. In the present study, we investigated whether PGE2 regulated interleukin (IL)-6 production in human gingival fibroblasts (HGF) stimulated with IL-1beta and if so, which subtype(s) of PGE2 receptors were involved. Indomethacin, a cyclooxygenase inhibitor, significantly enhanced IL-1beta-induced IL-6 production by HGF, although it completely inhibited IL-1beta-induced PGE2 production. Exogenous PGE2 suppressed the IL-1beta-induced IL-6 production. Reverse transcription-polymerase chain reaction analysis demonstrated that mRNA of EP1, EP2 and EP4, but not EP3 mRNA, was expressed in unstimulated and IL-1beta-stimulated HGF. 11-deoxy-PGE1, a selective EP2/EP3/EP4 agonist, and butaprost, a selective EP2 agonist, inhibited IL-1beta-induced IL-6 production, although butaprost was less potent than 11-deoxy-PGE1. 17-phenyl-omega-trinor PGE2, an EP1 agonist, enhanced IL-1beta-induced IL-6 production. Based on these data, we suggest that PGE2 can up- or downregulate IL-1beta-induced IL-6 production via EP1 receptors or via EP2/EP4 receptors in HGF, respectively. Expression and function of EP1, EP2 and EP4 receptors in HGF may play critical roles in controlling inflammatory periodontal conditions.
authors.affiliation: Department of Hard Tissue Engineering, Graduate School, Tokyo Medical & Dental University, Japan. kazuyuki-noguchi.peri@dent.tmd.ac.jp
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Noguchi
authors.forename: Miki
authors.initials: M
authors.lastname: Shitashige
authors.forename: Hirahito
authors.initials: H
authors.lastname: Endo
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Kondo
authors.forename: Isao
authors.initials: I
authors.lastname: Ishikawa
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic; D015854:Up-Regulation; D000093242:Interleukin-6 Inhibitors
chemical_list: D000527:Alprostadil; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007213:Indomethacin; D007375:Interleukin-1; D015850:Interleukin-6; D011459:Prostaglandins E, Synthetic; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000093242:Interleukin-6 Inhibitors; C092396:17-phenyltrinorprostaglandin E2; C545635:PTGER1 protein, human; C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; C545650:PTGER4 protein, human; C048491:butaprost; C034008:11-deoxyprostaglandin E1