STIM1 mediates IAV-induced inflammation of lung epithelial cells by regulating NLRP3 and inflammasome activation via targeting miR-223

Aims: Influenza A virus (IAV) infection accelerates the inflammatory injury of lung epithelial cells that contributes to pulmonary lesion. Recently, stromal interaction molecule 1 (STIM1) was found to mediate cellular immune response and participated in lung tumorigenesis. Our study aimed to illustrate the function and mechanism of STIM1 in IAV-induced inflammation injury and oxidative stress of lung epithelial cells. Main methods: We evaluated the levels of STIM1 in IAV-infected patients' serum and BEAS-2B cells using RTqPCR, Elisa and western blotting methods. MTT and Elisa were performed to measure cell viability and cytokine contents. Besides, ROS intensity, SOD contents and cell apoptosis were detected based on DCFH-DA probe, colorimetry and cell death kits. A luciferase assay and Pearson's correlation analysis evaluated the associations between target genes. Key findings: STIM1 was dramatically up-regulated in IAV-infected patients' serum and BEAS-2B cells. Silencing STIM1 in vitro inhibited oxidative stress and inflammatory responses induced by IAV, and reversed cell viability and suppressed apoptosis. Moreover, miR-223 and NLRP3 were negatively and positively correlated with STIM1. STIM1 was found to regulate NLRP3 expression by binding the AACUGAC motif in miR-223. STIM1/miR-223/NLRP3 axis modulated IAV-induced inflammation injury of lung epithelial cells. Significance: Our evidence indicated that silencing STIM1 alleviated IAV-induced inflammation injury of lung epithelial cells by inactivating NLRP3 and inflammasome via promoting miR-223 expression. These findings may contribute to understand the mechanism of IAV-induced lung injury and help for therapy of IAV infection.

Automated summary

The study showed that STIM1 was significantly up-regulated in IAV-infected patients' serum and BEAS-2B cells. Silencing STIM1 could inhibit oxidative stress and inflammatory responses induced by IAV, and miR-223/NLRP3 axis mediated the inflammation injury of lung epithelial cells induced by IAV.