Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany.
Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Mediators Inflamm. 2020 Feb 3;2020:4185273. doi: 10.1155/2020/4185273. eCollection 2020.
Periodontitis is a prevalent chronic inflammatory disease triggered by a synergistic and dysbiotic microbiota present in the oral biofilm. This in vitro study is aimed at evaluating the regulation of cyclooxygenase (COX)2 expression and production by the periodontopathogen in human gingival fibroblastic (HGF-1) and monocytic (THP-1) cells and also at investigating the underlying cellular pathway mechanisms. HGF-1 and THP-1 cells were exposed either to or to the proinflammatory cytokine tumor necrosis factor alpha (TNF) for 1 and 2 d to examine the COX2 expression by qPCR. COX2 protein levels were evaluated by ELISA in -stimulated cells. Both types of cells were also stimulated with a blocking toll-like receptor (TLR)2 antibody or specific inhibitors against MAPKs. significantly ( < 0.05) increased COX2 at both transcriptional and protein levels in both HGF-1 and THP-1 cells. Moreover, the stimulatory effect of on COX2 was more pronounced in HGF-1 cells in comparison to THP-1 cells. upregulated the COX2 expression in a dose-dependent manner in both type cells at 1 d. TNF also significantly ( < 0.05) increased the COX2 expression in both cells. After preincubation of HGF-1 and THP-1 cells either with a neutralizing anti-TLR2 antibody or with specific MAPK inhibitors, the -upregulated COX2 expression was significantly ( < 0.05) suppressed at 1 d. Our in vitro study provides original evidence that stimulates COX2 production in fibroblastic and monocytic cells through TLR2 and MAPK mechanisms, suggesting a role of this periodontopathogen in the etiopathogenesis of periodontitis.
牙周炎是一种由口腔生物膜中协同失调的微生物群落引发的普遍慢性炎症性疾病。本体外研究旨在评估牙周病原菌对人牙龈成纤维细胞（HGF-1）和单核细胞（THP-1）细胞中环氧化酶（COX）2表达和产生的调节作用，并研究其潜在的细胞通路机制。将 HGF-1 和 THP-1 细胞暴露于或促炎细胞因子肿瘤坏死因子-α（TNF）中 1 和 2 天，以通过 qPCR 检测 COX2 表达。通过 ELISA 评估 - 刺激细胞中的 COX2 蛋白水平。用阻断 Toll 样受体（TLR）2 抗体或针对 MAPK 的特异性抑制剂刺激两种类型的细胞。在 HGF-1 和 THP-1 细胞中，均显著（<0.05）增加了 COX2 的转录和蛋白水平。此外，与 THP-1 细胞相比，在 HGF-1 细胞中，对 COX2 的刺激作用更为明显。在两种类型的细胞中，在 1 天内以剂量依赖的方式上调 COX2 表达。TNF 也显著（<0.05）增加了两种细胞的 COX2 表达。在用中和抗 TLR2 抗体或特定 MAPK 抑制剂预先孵育 HGF-1 和 THP-1 细胞后，在 1 天内，- 上调的 COX2 表达被显著（<0.05）抑制。我们的体外研究提供了原始证据，表明通过 TLR2 和 MAPK 机制刺激成纤维细胞和单核细胞中 COX2 的产生，表明该牙周病原菌在牙周炎的发病机制中起作用。
