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

环氧合酶2在牙周病发病机制中的作用

• 批准号: 07672073
• 负责人: NOGUCHI Kazuyuki
• 金额: $ 1.54万
• 依托单位: Tokyo Medical & Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672073/
• 关键词: periodontal disease; gingival fibroblast; periodontal ligament cells; prostaglandin E_2; cyclooxygenase-2; LPS; interleukin-1; Th2 cytokine; IL-1β; MMP-1; IL-x; IL-13; EPレセプター; IL-1α; IL-4; PGE_2; COX-2; 単球; シクロオキシゲナーゼ-ス; インターロイキン-1β

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.

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。

项目成果

K.Noguchi et al.: "PROSTAGLANDIN PRODUCTION VIA INDUCTION OF CYCLOOXYGENASE-2 BY HUMAN GINGIVAL FIBROBLASTS STIMULATED WITH LIPOPYSACCHARIDES" Inflammation. 20・5. 555-568 (1996)

K.Noguchi 等：“通过脂质体刺激的人牙龈成纤维细胞诱导环加氧酶 2 产生前列腺素”炎症。 555-568。

K.Noguchi: "Prostaglandin production via cyclooxygenase-2 by human gingival fibroblasts stimulated with lipopolysaccharides" Inflammation. 20 (5). 555-568 (1996)

K.Noguchi：“脂多糖刺激的人牙龈成纤维细胞通过环氧合酶 2 产生前列腺素”炎症。

I.Morita: "Pain and prostaglandins" Sogo Rinsho. 44 (10). 2379-2383 (1995)

I.Morita：“疼痛和前列腺素”Sogo Rinsho。

I.Ishikawa,K.Noguchi et al.(Edited by P.M.Bartold): "RISK FACTORS IN ASIAN PACIFIC POPULATIONS" Asian Pacific Society of Periodontology, 174 (1996)

I.Ishikawa,K.Noguchi 等人（P.M.Bartold 编辑）：“亚太地区人口的风险因素”亚太牙周病学会，174 (1996)

K.Noguchi: "Prastaglandin production via inductionof cyclooxygenase-2 by human gingival fibroblasts stimulated with lipopolysaccharides" Inflammation. 20(5). 555-568 (1996)

K.Noguchi：“脂多糖刺激的人牙龈成纤维细胞通过诱导环氧合酶 2 产生前列腺素”炎症。