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Mechanism of Notch Signal Regulating Alveolar Epithelial Cell Autophagy after Infection with Klebsiella Pneumoniae by Zhiyun Shi, Xiaoli Yin, Xiaohui Hou, Liangfang Wang, Gang Li, Juying Wang, Wen Wang, Yuying Zhang, Shasha Li, Wei Jia

Background: The Notch signaling pathway regulates various cellular processes, including cell growth, inflammation response, and autophagy, thereby participating in the occurrence and development of various diseases. The present study aimed to investigate the molecular mechanism of Notch signaling in regulating alveolar type II epithelial cell viability and autophagy after Klebsiella pneumonia (KPN) infection.
Methods: KPN-infected human alveolar type II epithelial cells A549 (ACEII) were constructed. The autophagy inhibitor 3-methyladenine (3-MA) and Notch1 signaling inhibitor (DAPT) were used to pretreat A549 cells for 24 hours, 48 hours, and 72 hours before KPN infection. Real-time fluorescent quantitative PCR (qRT-PCR) and western blot assays were applied to detect the mRNA and protein expressions of LC3 and Notch1, respectively. ELISA was used to detect the levels of INF-γ, TNF-α, and IL-1β in the cell supernatants.
Results: The results showed that KPN-infected A549 cells presented significantly upregulated Notch1 and autophagy-related protein LC3 levels, along with increased IL-1β, TNF-α, INF-γ levels in a time-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) counteracted the promotive effects of LC3 and inflammatory cytokine levels in KPN-infected A549 cells; however, 3-MA did not influence Notch1 level. Notch1 inhibitor DAPT could suppress Notch1 and LC3 levels, thereby inhibiting inflammation response in KPN-treated A549 cells in a time-dependent way.
Conclusions: KPN infection can activate the Notch signaling pathway and induce autophagy in type Ⅱ alveolar epithelial cells. Inhibiting the Notch signaling pathway may restrain KPN-induced A549 cell autophagy and inflammation response, shedding new insights for the treatment of pneumonia.

DOI: 10.7754/Clin.Lab.2022.211203