P. gingivalis (Pg) is an oral pathogen with the ability to induce oral dysbiosis and periodontal disease. Nevertheless, the mechanisms by which mucosal responses to the oral microbiota in the presence of specific pathogens such as Pg could abrogate the host-microbe symbiotic relationship leading to periodontitis remain unclear. Herein, we identified the Notch-1/PLA₂-IIA axis as a new molecular pathway through which Pg could be specifically modulating oral epithelial antimicrobial and inflammatory responses. Pg activated Notch-1, and inhibition or silencing of Notch-1 completely abrogated Pg-induced PLA₂-IIA in oral epithelial cells (OECs). Activation of Notch-1 and PLA₂-IIA production were associated with Pg-produced gingipains. Other oral Gram-positive and Gram-negative species failed to induce similar responses. Pg enhanced OEC antimicrobial activity through PLA₂-IIA. Increased Notch-1 activation correlated with higher PLA₂-IIA gingival expression and changes in the abundance of specific oral bacteria phyla during periodontal disease. Oral bacterial species exhibited differential antimicrobial susceptibility to PLA₂-IIA. These findings support previous evidence suggesting an important role for epithelial Notch-1 activation and PLA₂-IIA production during health and disease at mucosal surfaces, and provide new mechanistic information concerning the regulation of epithelial antimicrobial and pro-inflammatory responses modulated by oral pathogenic bacteria associated with periodontal disease.

中文翻译：

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牙龈卟啉单胞菌激活口腔上皮细胞中的 Notch-1 会触发抗菌蛋白 PLA2-IIA 的表达。

牙龈卟啉单胞菌 (Pg) 是一种口腔病原体，能够诱发口腔生态失调和牙周病。然而，在存在特定病原体（如 Pg）的情况下，粘膜对口腔微生物群的反应可能会破坏导致牙周炎的宿主-微生物共生关系的机制仍不清楚。在此，我们将 Notch-1/PLA ₂ -IIA 轴确定为一种新的分子通路，Pg 可通过该通路特异性调节口腔上皮抗菌和炎症反应。Pg 激活 Notch-1，抑制或沉默 Notch-1 可完全消除口腔上皮细胞 (OEC) 中 Pg 诱导的 PLA ₂ -IIA。Notch-1 和 PLA _2的激活-IIA 生产与 Pg 生产的牙龈蛋白酶有关。其他口服革兰氏阳性和革兰氏阴性物种未能引起类似的反应。_{Pg 通过 PLA 2} -IIA增强 OEC 抗菌活性。增加的 Notch-1 激活与更高的 PLA ₂ -IIA 牙龈表达和牙周病期间特定口腔细菌门的丰度变化相关。口腔细菌种类对 PLA ₂ -IIA 表现出不同的抗菌敏感性。_{这些发现支持先前的证据表明上皮 Notch-1 激活和 PLA 2}具有重要作用-IIA 在健康和疾病期间在粘膜表面的产生，并提供有关由与牙周病相关的口腔致病菌调节的上皮抗菌和促炎反应的调节的新机制信息。