Resumen de Interleukin-1β–Induced Prostaglandin E2 Production by Human Gingival Fibroblasts Is Upregulated by Glycine

Dr. Xiaohui Rausch-Fan, Christian Ulm, Wolf-Dieter Rausch, Michael Matejka

• Background: Human gingival fibroblasts (GFB) may produce prostaglandin E2 (PGE2) 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 PGE2 production.

  Methods: Human GFB were cultured in the presence of various concentrations of glycine and/or interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-10 and their influence on PGE2 production was measured. The expression of cyclooxygenases (COX) was analyzed by Western blot and immunocytochemistry.

  Results: The PGE2 production by IL-1β-stimulated GFB was significantly upregulated by glycine. The effect of glycine on IL- 1β-induced cell proliferation and PGE2 production was concentration- dependent, reached a peak at 3 mM, and declined slowly at higher doses. The synthesis of PGE2 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-α-induced PGE2 production. The IL-1β-driven PGE2 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-1β, and mostly enhanced by combined IL-1β with glycine.

  Conclusion: Since PGE2 is a potent stimulator of bone resorption, and production of PGE2 and COX-2 protein is augmented by glycine, our results strongly suggest that glycine may be involved in the pathogenesis of periodontitis. J Periodontol 2005;76:1182-1188.