Periodontal Treatment Downregulates Protease-Activated Receptor 2 in Human Gingival Crevicular Fluid Cells
Periodontal Treatment Downregulates Protease-Activated Receptor 2 in Human Gingival Crevicular Fluid Cells
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DOI：
10.1128/iai.01107-13
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发表时间：
2013-12-01
影响因子：
3.1
通讯作者：
Holzhausen, Marinella
中科院分区：
文献类型：
--
作者：
Euzebio Alves, Vanessa Tubero;Bueno da Silva, Henrique Aparecido;Holzhausen, Marinella
蛋白酶激活受体2（PAR 2）与慢性炎症性疾病（包括牙周炎）的发病机制有关;它可以被牙龈卟啉菌蛋白酶激活并由牙龈卟啉单胞菌和中性粒细胞蛋白酶3（P3）产生。PAR 2激活通过诱导与牙周分解相关的重要炎症介质的释放，在炎症过程中发挥相关作用。研究了牙周治疗对慢性牙周炎患者PAR 2表达的影响及其与促炎介质和活化蛋白酶水平的相关性。在龈沟液细胞中观察到PAR 2阳性染色，反映了组织破坏。PAR 2的过度表达与炎症临床参数以及白细胞介素-6（IL-6）、IL-8、肿瘤坏死因子α、基质金属蛋白酶2（MMP-2）、MMP-8、肝细胞生长因子和血管内皮生长因子的水平呈正相关。牙龈菌蛋白酶和P3水平升高，牙本质素和蛋白酶抑制剂分泌性白细胞蛋白酶抑制剂和弹性蛋白酶水平降低也与PAR 2过表达相关。慢性牙周炎患者正常牙周组织中PAR 2 mRNA和蛋白的表达均较正常牙周组织明显降低（P < 0.05）。此外，牙周治疗导致PAR 2表达降低，并与炎症介质和活化蛋白酶的表达降低相关。我们的结论是，牙周治疗导致蛋白酶水平下降，促炎介质与PAR 2表达下降，表明PAR 2表达的影响牙周感染的存在，并不是有利于牙周炎症的组成特征。
Protease-activated receptor 2 (PAR2) is implicated in the pathogenesis of chronic inflammatory diseases, including periodontitis; it can be activated by gingipain and produced by Porphyromonas gingivalis and by neutrophil protease 3 (P3). PAR2 activation plays a relevant role in inflammatory processes by inducing the release of important inflammatory mediators associated with periodontal breakdown. The effects of periodontal treatment on PAR2 expression and its association with levels of proinflammatory mediators and activating proteases were investigated in chronic periodontitis patients. Positive staining for PAR2 was observed in gingival crevicular fluid cells and was reflective of tissue destruction. Overexpression of PAR2 was positively associated with inflammatory clinical parameters and with the levels of interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha, matrix metalloprotease 2 (MMP-2), MMP-8, hepatocyte growth factor, and vascular endothelial growth factor. Elevated levels of gingipain and P3 and decreased levels of dentilisin and the protease inhibitors secretory leukocyte protease inhibitor and elafin were also associated with PAR2 overexpression. Healthy periodontal sites from individuals with chronic periodontitis showed diminished expression of PAR2 mRNA and the PAR2 protein (P < 0.05). Furthermore, periodontal treatment resulted in decreased PAR2 expression and correlated with decreased expression of inflammatory mediators and activating proteases. We concluded that periodontal treatment resulted in decreased levels of proteases and that proinflammatory mediators are associated with decreased PAR2 expression, suggesting that PAR2 expression is influenced by the presence of periodontal infection and is not a constitutive characteristic favoring periodontal inflammation.