title: Expression of prostaglandin E synthases in periodontitis immunolocalization and cellular regulation.
abstract: The inflammatory mediator prostaglandin E(2) (PGE(2)) is implicated in the pathogenesis of chronic inflammatory diseases including periodontitis; it is synthesized by cyclooxygenases (COX) and the prostaglandin E synthases mPGES-1, mPGES-2, and cPGES. The distribution of PGES in gingival tissue of patients with periodontitis and the contribution of these enzymes to inflammation-induced PGE(2) synthesis in different cell types was investigated. In gingival biopsies, positive staining for PGES was observed in fibroblasts and endothelial, smooth muscle, epithelial, and immune cells. To further explore the contribution of PGES to inflammation-induced PGE(2) production, in vitro cell culture experiments were performed using fibroblasts and endothelial, smooth muscle, and mast cells. All cell types expressed PGES and COX-2, resulting in basal levels of PGE(2) synthesis. In response to tumor necrosis factor (TNF-α), IL-1β, and cocultured lymphocytes, however, mPGES-1 and COX-2 protein expression increased in fibroblasts and smooth muscle cells, accompanied by increased PGE(2), whereas mPGES-2 and cPGES were unaffected. In endothelial cells, TNF-α increased PGE(2) production only via COX-2 expression, whereas in mast cells the cytokines did not affect PGE(2) enzyme expression or PGE(2) production. Furthermore, PGE(2) production was diminished in gingival fibroblasts derived from mPGES-1 knockout mice, compared with wild-type fibroblasts. These results suggest that fibroblasts and smooth muscle cells are important sources of mPGES-1, which may contribute to increased PGE(2) production in the inflammatory condition periodontitis.
authors: Division of Pediatric Dentistry, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Tove
authors: T
authors: Båge
authors: Anna
authors: A
authors: Kats
authors: Blanca Silva
authors: BS
authors: Lopez
authors: Gareth
authors: G
authors: Morgan
authors: Gunnar
authors: G
authors: Nilsson
authors: Idil
authors: I
authors: Burt
authors: Marina
authors: M
authors: Korotkova
authors: Lisa
authors: L
authors: Corbett
authors: Alan J
authors: AJ
authors: Knox
authors: Leonardo
authors: L
authors: Pino
authors: Per-Johan
authors: PJ
authors: Jakobsson
authors: Thomas
authors: T
authors: Modéer
authors: Tülay
authors: T
authors: Yucel-Lindberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005881:Gingiva / Q000196:embryology / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010518:Periodontitis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; C000605863:PTGES2 protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; C000605866:Ptges2 protein, mouse