Porphyromonas gulae, a Gram‐negative black‐pigmented anaerobe, has been associated with periodontal disease in companion animals and its virulence has been attributed to various factors, including lipopolysaccharide (LPS), protease and fimbriae. Toll‐like receptors (TLRs) recognise pathogen‐associated molecular patterns, such as peptidoglycan, lipids, lipoproteins, nucleic acid and LPS. Following P. gulae infection, some inflammatory responses are dependent on both TLR2 and TLR4. In addition, a recent clinical study revealed that acute and persistent inflammatory responses enhance the expressions of TLR2 and TLR4 in the oral cavity. In this study, we investigated the interaction between P. gulae LPS and human gingivalis epithelial cells (Ca9‐22 cells). P. gulae LPS was found to increase TLR2 and TLR4 mRNA expressions and protein productions, and enhanced inflammatory responses, such as COX₂, TNF‐ɑ, IL‐6 and IL‐8. Stimulated Ca9‐22 cells exhibited phosphorylation of ERK1/2 and p38, and their inhibitors diminished inflammatory responses, while knockdown of the TLR2 and/or TLR4 genes with small interfering RNA (siRNA) prevented inflammatory responses. Moreover, p38 and ERK1/2 phosphorylation was decreased in TLR2 and TLR4 gene knockdown cells. These findings suggest that P. gulae LPS activates p38 and ERK1/2 via TLR2 and TLR4, leading to inflammatory responses in human gingival epithelial cells.

中文翻译：

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古拉卟啉单胞菌脂多糖通过人牙龈上皮细胞中的 toll 样受体 2 和 4 引发炎症反应。

古拉卟啉单胞菌是一种革兰氏阴性黑色色素厌氧菌，与伴侣动物的牙周病有关，其毒力可归因于多种因素，包括脂多糖 (LPS)、蛋白酶和菌毛。Toll 样受体 (TLR) 识别病原体相关的分子模式，如肽聚糖、脂质、脂蛋白、核酸和 LPS。跟随P。gulae感染，一些炎症反应依赖于 TLR2 和 TLR4。此外，最近的一项临床研究表明，急性和持续性炎症反应增强了口腔中 TLR2 和 TLR4 的表达。在这项研究中，我们调查了P之间的相互作用。古莱LPS 和人牙龈上皮细胞（Ca9-22 细胞）。P。发现gulae LPS 增加TLR2和TLR4 mRNA 表达和蛋白质产生，并增强炎症反应，如 COX ₂、TNF-ɑ、IL-6 和 IL-8。受刺激的 Ca9-22 细胞表现出 ERK1/2 和 p38 的磷酸化，它们的抑制剂减弱了炎症反应，而用小干扰 RNA (siRNA)敲低TLR2和/或TLR4基因则阻止了炎症反应。此外，在TLR2和TLR4基因敲低细胞中，p38 和 ERK1/2 磷酸化降低。这些发现表明P. gulae LPS 通过 TLR2 和 TLR4 激活 p38 和 ERK1/2，导致人牙龈上皮细胞的炎症反应。