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Interleukin-1beta-induced prostaglandin E2 production by human gingival fibroblasts is upregulated by glycine.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsXiaohui Rausch-Fan, Christian Ulm, Erika Jensen-Jarolim, Andreas Schedle, George Boltz-Nitulescu, Wolf-Dieter Rausch, Michael Matejka
JournalJournal of periodontology (J Periodontol) Vol. 76 Issue 7 Pg. 1182-8 (Jul 2005) ISSN: 0022-3492 [Print] United States
PMID16018763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Interleukin-1
  • Membrane Proteins
  • Nitrobenzenes
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Interleukin-10
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Glycine
  • Indomethacin
Topics
  • Analysis of Variance
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors (pharmacology)
  • Dinoprostone (analysis, antagonists & inhibitors, biosynthesis)
  • Dose-Response Relationship, Drug
  • Fibroblasts (drug effects, metabolism)
  • Gingiva (cytology, drug effects, metabolism)
  • Glycine (metabolism, pharmacology)
  • Humans
  • Indomethacin (pharmacology)
  • Interleukin-1 (pharmacology)
  • Interleukin-10 (pharmacology)
  • Membrane Proteins
  • Nitrobenzenes (pharmacology)
  • Periodontal Diseases (immunology, microbiology)
  • Prostaglandin-Endoperoxide Synthases (biosynthesis)
  • Sulfonamides (pharmacology)
  • Up-Regulation

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