Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.
Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.
Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China. jchsmg@fmmu.edu.cn
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Guan
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Fu
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He
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Zhang
D018929:Cell Culture Techniques; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009578:Nitrobenzenes / Q000494:pharmacology; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018713:Prevotella intermedia / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000037:antagonists & inhibitors; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D009578:Nitrobenzenes; D000081082:Phosphoinositide-3 Kinase Inhibitors; 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; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D007213:Indomethacin