The roles of cyclooxygenase-2 in the pathogenesis of periodontal disease

1. 研究了环加酶-1 (COX-1) 和环加氧酶-2 (COX-2) 在牙周病细菌刺激的人牙龈成纤维细胞 (HGF) 产生前列腺素 E_2 (PGE_2) 过程中的参与情况。制备从牙龈卟啉单胞菌（P.gingivalis）和伴放线放线杆菌（A.actinomycetemcomitans）分离的脂多糖。 LPS制剂以剂量和时间依赖性方式产生PGE_2。 P.gingivalis-LPS 是比 A.actinomycetemcomitans-LPS 更有效的刺激剂。用选择性 COX 抑制剂 NS-398 处理细胞，完全抑制 PGE_2 的产生。 COX-2免疫组化染色显示P.gingivalis-LPS处理后24 h COX-2蛋白表达增加。酪氨酸激酶抑制剂处理后COX-2表达受到抑制，提示酪氨酸激酶参与COX-2表达。Th2细胞因子白细胞介素(IL)-4和-13对IL-1α刺激牙周膜产生PGE_2的影响(PDL) 细胞进行了研究。用IL-4和-13处理IL-1α细胞以剂量依赖性方式抑制PGE_2产生。 IL-4 和-13 抑制COX-2 mRNA 表达。推测IL-4和-13通过COX-2的表达调节IL-1α刺激的PDL细胞产生PGE_2。 3．研究了IL-1β刺激的HGF对PGE_2对基质金属蛋白酶-1 (MMP-1)的影响。用 NS-398 处理细胞增强了 MMP-1 的产生，外源添加 PEG_2 也抑制了 MMP-1 的产生。数据表明PGE_2通过IL-1β刺激的HGF调节MMP-1的产生。用IL-4和-13处理细胞通过抑制PGE_2的产生来增强MMP-1的产生。

1. The involvement of cycloocygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin E_2 (PGE_2) production by human gingival fibroblasts (HGF) stimulated with periodontpathic bacteria was investigated. Lipopolysaccharides isolated from Porphyromonas gingivalis (P.gingivalis) and Actinobacillus actinomycetemcomitants (A.actinomycetemcomitans) were prepared. The LPS preparations produced PGE_2 in a dose- and time-dependent manner. P.gingivalis-LPS was a more potent stimulator than A.actinomycetemcomitans-LPS.Treatment of the cells with NS-398, a selective COX-inhibitor, completely suppresed PGE_2 production. Immunohistochemical staining of COX-2 showed that COX-2 protein expression was increased 24 h after P.gingivalis-LPS.The COX-2 expression was inhibted by treatment with tyrosine kinase inhibitors, which suggested that tyrosine kinase was involved in COX-2 expression.The effect of Th2 cytokines, interleukin (IL)-4 and -13, on PGE_2 production by IL-1alpha-stimulated periodontal ligament (PDL) cells was studied. Treatment of the IL-1alpha-cells with IL-4 and -13 inhibited PGE_2 production in a dose-dependent manner. IL-4 and -13 suppressed COX-2 mRNA expression. It was suggested that IL-4 and -13 regulate PGE_2 production by IL-1alpha-stimulatedPDL cells, through COX-2 expression.3. The effect of PGE_2 on matrix metalloproteinase-1 (MMP-1) by IL-1beta-stimulated HGF was investigated. Treatment of the cells with NS-398 enhanced MMP-1 generation and exogenous addition of PEG_2 also inhibited MMP-1 production. The data suggested that PGE_2 regulated MMP-1 production by IL-1beta-stimulated HGF.Treatment of the cells with IL-4 and -13 enhanced MMP-1 production, by inhibiting PGE_2 production.