Zhang Diya, Li Shenglai, Hu Lingjing, Sheng Lieping, Chen Lili
Dental Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
Department of Oral and Maxillofacial Surgery, Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China.
BMC Oral Health. 2015 Oct 17;15(1):128. doi: 10.1186/s12903-015-0105-8.
Protease-activated receptors (PARs) are G-protein-coupled receptors with an active role in mediating inflammation, pain and other functions. The oral pathogen Porphyromonas gingivalis (P. gingivalis) secretes proteases that activate PARs. The aim of this study was to elucidate the role of PARs in the pathogenesis of chronic periodontitis by expression analysis of PARs in human gingival epithelial cells (GECs) before and after P. gingivalis supernatants treatment.
GECs were isolated from healthy human gingival tissue samples. The expression of PARs in GECs was determined by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. The effect of P. gingivalis proteases was investigated by quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR) and flow cytometry.
PAR-1, PAR-2, and PAR-3 were expressed in GECs. PAR-4 was not found by both RT-PCR and flow cytometry. Analysis of gene expression using QRT-PCR showed an up-regulation of PAR-2 mRNA in comparison to the untreated control cells (P < 0.05). In contrast, the mRNA expressions of PAR-1 and PAR-3 were significantly down-regulated (P > 0.05) in response to P. gingivalis supernatant compared to that in unstimulated control cells. This effect was abrogated by the protease inhibitor TLCK (P < 0.05). The results of flow cytometry indicated PARs protein levels consistent with mRNA levels in the results of QRT-PCR.
Our study shows that PAR-1, PAR-2 and PAR-3 are expressed in GECs. P. gingivalis proteases play a role in the regulation of innate immune responses in GECs. GECs use PARs to recognize P. gingivalis and mediate cell responses involved in innate immunity.
蛋白酶激活受体(PARs)是G蛋白偶联受体,在介导炎症、疼痛和其他功能中发挥积极作用。口腔病原体牙龈卟啉单胞菌(P. gingivalis)分泌激活PARs的蛋白酶。本研究的目的是通过分析牙龈卟啉单胞菌上清液处理前后人牙龈上皮细胞(GECs)中PARs的表达,阐明PARs在慢性牙周炎发病机制中的作用。
从健康人牙龈组织样本中分离GECs。通过逆转录聚合酶链反应(RT-PCR)和流式细胞术测定GECs中PARs的表达。采用定量实时逆转录聚合酶链反应(QRT-PCR)和流式细胞术研究牙龈卟啉单胞菌蛋白酶的作用。
GECs中表达PAR-1、PAR-2和PAR-3。RT-PCR和流式细胞术均未检测到PAR-4。使用QRT-PCR分析基因表达显示,与未处理的对照细胞相比,PAR-2 mRNA上调(P < 0.05)。相反,与未刺激的对照细胞相比,牙龈卟啉单胞菌上清液处理后PAR-1和PAR-3的mRNA表达显著下调(P > 0.05)。蛋白酶抑制剂TLCK可消除这种作用(P < 0.05)。流式细胞术结果表明PARs蛋白水平与QRT-PCR结果中的mRNA水平一致。
我们的研究表明PAR-1、PAR-2和PAR-3在GECs中表达。牙龈卟啉单胞菌蛋白酶在调节GECs的固有免疫反应中发挥作用。GECs利用PARs识别牙龈卟啉单胞菌并介导参与固有免疫的细胞反应。