Involvement of Cyclooxygenase‐2 in Interleukin‐1α‐Induced Prostaglandin Production by Human Periodontal Ligament Cells

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Abstract
Background: Human periodontal ligament (PDL) cells produce prostaglandin (PG) E2 in response to proinflammatory cytokines. However, the mechanism of PGE2 production is not well understood. The purpose of the present study was to investigate the involvement of cyclooxygenase (COX)‐1 and COX‐2 in PGE, production by PDL cells to examine the regulation of PGE2 production by cell‐cell interaction of human gingival keratinocytes and PDL cells. stimulated with a proinflammatory cytokine, interleukin‐1 α (IL‐1 α ), andMethods: The levels of PGE2 in the culture media of PDL cells stimulated with IL‐1 α or culture media of human gingival keratinocytes were determined by an enzyme‐linked immunosorbent assay. Expression of COX‐1 and ‐2 mRNA and protein was studied by Northern blot analysis and Western blot analysis, respectively.Results: IL‐1 α ‐stimulated PDL cells produced PGE2 in a time‐dependent manner. Indomethacin, a non‐selective COX‐1/COX‐2 inhibitor, and NS‐398, a selective COX‐2 inhibitor, completely inhibited PGE2 production by the IL‐1 α ‐stimulated cells. COX‐2 mRNA was detected after IL‐1 α stimulation, although it was not detected in unstimulated cells. There was no difference in expression of COX‐1 mRNA between unstimulated cells and IL‐1 α ‐stimulated cells. Expression of COX‐2 protein in IL‐1 α ‐stimulated cells was increased, compared with that in unstimulated cells, whereas COX‐1 protein expression was almost the same in both the cells. Treatment of IL‐1 α ‐stimulated PDL cells with dexamethasone, known to inhibit COX‐2 expression, prevented PGE2 production and COX‐2 mRNA expression. Addition of the culture media of human gingival keratinocytes to PDL cells increased PGE2 production. The PGE2 production was depressed by treatment of the cells with IL‐1 receptor antagonist and anti‐ IL‐1 α antibody, not with anti‐IL‐1β antibody. The PGE2 production was also inhibited by treatment with NS‐398 and dexamethasone.Conclusions: We suggest that PDL cells stimulated with IL‐1 α produce PGE2 through de novo synthesis of COX‐2 and that the cell interaction of gingival keratinocytes and PDL cells controls COX‐2 expression and PGE2 production via IL‐1 α or a IL‐1 α ‐like factor(s). Selective COX‐2 inhibitors, which have the advantage of reduced gastric toxicity, may provide a useful approach to treatment of periodontal disease. J Periodontol 1999; 70:902‐908.