title: C2-ceramide inhibits the prostaglandin E2-induced accumulation of cAMP in human gingival fibroblasts.
abstract: Ceramide is generated by the hydrolysis of membrane sphingomyelin by sphingomyelinase and is implicated in multiple signaling pathways, including those regulating differentiation, inflammation and immune responses. Excess formation of prostaglandin E(2) (PGE(2)) is thought to increase susceptibility to infection, rheumatoid arthritis and inflammation, including periodontal diseases. We investigated the inhibitory effect of C(2)-ceramide, a short-chain ceramide analog, on the PGE(2)-stimulated accumulation of cAMP in human gingival fibroblasts. In human gingival fibroblasts pre-treated with C(2)-ceramide for 18 h, the PGE(2)-stimulated accumulation of cAMP was reduced, but an inactive C(2)-ceramide analog had no such effect. The accumulation of cAMP induced by EP2 and EP4 receptor agonists (ONO-AE1-259 and ONO-AE1-329, respectively) was inhibited in cells treated with C(2)-ceramide. However, treatment with C(2)-ceramide had no effect on the expression of mRNAs encoding the EP2 and EP4 receptors. Accumulation of cAMP could be induced by cAMP-elevating agents (forskolin, isobutylmethylxanthine and mastparan) but was not reduced by treatment with C(2)-ceramide. These observations suggest that C(2)-ceramide attenuates PGE(2) receptor function and consequently inhibits the accumulation of cAMP in human gingival fibroblasts.
authors.affiliation: Department of Oral Molecular Pharmacology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. nakao.sumi@nihon-u.ac.jp
authors.forename: Sumi
authors.initials: S
authors.lastname: Nakao
authors.forename: Seiko
authors.initials: S
authors.lastname: Moriyama
authors.forename: Masaomi
authors.initials: M
authors.lastname: Segawa
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Guo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiya
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008738:Methyl Ethers; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism / Q000494:pharmacology; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015398:Signal Transduction / Q000187:drug effects; D013109:Sphingomyelins / Q000378:metabolism / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives
chemical_list: C499423:9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2; D002518:Ceramides; D008738:Methyl Ethers; C064769:N-acetylsphingosine; C461399:ONO-AE1-329; C545650:PTGER4 protein, human; D011458:Prostaglandins E; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013109:Sphingomyelins; D005576:Colforsin; D015232:Dinoprostone; D013110:Sphingosine