title: Interleukin-1beta-induced prostaglandin E2 production by human gingival fibroblasts is upregulated by glycine.
abstract: BACKGROUND
  Human gingival fibroblasts (GFB) may produce prostaglandin E(2) (PGE(2)) in response to proinflammatory cytokines. Elevated concentrations of glycine were previously found in periodontal pockets and saliva of periodontitis patients and, therefore, we aimed to study the influence of glycine on PGE(2) production.
  
  
  METHODS
  Human GFB were cultured in the presence of various concentrations of glycine and/or interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-10 and their influence on PGE(2) production was measured. The expression of cyclooxygenases (COX) was analyzed by Western blot and immunocytochemistry.
  
  
  RESULTS
  The PGE(2) production by IL-1beta-stimulated GFB was significantly upregulated by glycine. The effect of glycine on IL- 1beta-induced cell proliferation and PGE(2) production was concentration- dependent, reached a peak at 3 mM, and declined slowly at higher doses. The synthesis of PGE(2) by human GFB cultured in the absence of glycine was significantly inhibited by IL-10 and partially induced in cells cultured with glycine. Glycine had no effect on TNF-alpha-induced PGE(2) production. The IL-1beta-driven PGE(2) synthesis was blocked by indomethacin, a COX-1/COX-2 inhibitor, and by COX-2 inhibitor NS-398. The expression of COX-2 protein was slightly induced by glycine, more evidently by IL-1beta, and mostly enhanced by combined IL-1beta with glycine.
  
  
  CONCLUSIONS
  Since PGE(2) is a potent stimulator of bone resorption, and production of PGE(2) and COX-2 protein is augmented by glycine, our results strongly suggest that glycine may be involved in the pathogenesis of periodontitis.
authors: Department of Periodontology, Dental School, Medical University Vienna, Waehringer Strasse 25A, A-1090 Vienna, Austria. xiaohui.rausch@meduniwien.ac.at
authors: Xiaohui
authors: X
authors: Rausch-Fan
authors: Christian
authors: C
authors: Ulm
authors: Erika
authors: E
authors: Jensen-Jarolim
authors: Andreas
authors: A
authors: Schedle
authors: George
authors: G
authors: Boltz-Nitulescu
authors: Wolf-Dieter
authors: WD
authors: Rausch
authors: Michael
authors: M
authors: Matejka
mesh_terms: D000704:Analysis of Variance; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D010510:Periodontal Diseases / Q000276:immunology / Q000382:microbiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016753:Interleukin-10; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D005998:Glycine; D007213:Indomethacin