Interleukin-1beta-induced prostaglandin E2 production by human gingival fibroblasts is upregulated by glycine.
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.
Rausch-Fan
Xiaohui
X
Department of Periodontology, Dental School, Medical University Vienna, Waehringer Strasse 25A, A-1090 Vienna, Austria. xiaohui.rausch@meduniwien.ac.at
Ulm
Christian
C
Jensen-Jarolim
Erika
E
Schedle
Andreas
A
Boltz-Nitulescu
George
G
Rausch
Wolf-Dieter
WD
Matejka
Michael
M
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
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