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

1. 研究了环氧化酶-1 （COX-1）和环氧化酶-2 （COX-2）在牙周病细菌刺激下牙龈成纤维细胞（HGF）分泌前列腺素e2 （PGE_2）过程中的作用。从牙龈卟啉单胞菌（P.gingivalis）和放线菌comitans （A.actinomycetemcomitans）中分离得到脂多糖。LPS制备的PGE_2具有剂量依赖性和时间依赖性。P.gingivalis-LPS比a .放线菌comitans- lps具有更强的刺激作用。选择性cox -抑制剂NS-398完全抑制了PGE_2的产生。免疫组化COX-2染色显示，P.gingivalis-LPS后24 h COX-2蛋白表达升高。酪氨酸激酶抑制剂可抑制COX-2的表达，提示酪氨酸激酶参与COX-2的表达。研究了Th2细胞因子白细胞介素-4和-13对IL-1刺激牙周韧带细胞生成PGE_2的影响。用IL-4和-13处理il -1 α -细胞可抑制PGE_2的产生，并呈剂量依赖性。IL-4和-13抑制COX-2 mRNA的表达。提示IL-4和-13通过表达COX-2调控il -1 α刺激的pdl细胞生成PGE_2。研究了PGE_2对il -1 β刺激HGF的基质金属蛋白酶-1 （MMP-1）的影响。NS-398处理能促进MMP-1的生成，外源添加PEG_2也能抑制MMP-1的产生。数据表明PGE_2调节il -1 β刺激的HGF产生MMP-1。IL-4和-13处理细胞通过抑制PGE_2的产生来促进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.