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

Abstract

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 RT-qPCR, 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.

• Authors: Cui-Cui Liu, Yi Miao, Rui-Lin Chen, Yong-Qing Zhang, Hua Wu, Shu-Mei Yang, Li-Qun Shang
• Journal: Life sciences (Life Sci) Vol. 266 Pg. 118845 (Feb 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33278394 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Inflammasomes
• MIRN223 microRNA, human
• MicroRNAs
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Neoplasm Proteins
• STIM1 protein, human
• Stromal Interaction Molecule 1

Topics

• Adult
• Apoptosis
• Case-Control Studies
• Cell Survival
• Cytokines (metabolism)
• Epithelial Cells (immunology, metabolism, pathology, virology)
• Female
• Humans
• Inflammasomes (metabolism)
• Inflammation (etiology, metabolism, pathology)
• Influenza A virus (isolation & purification)
• Influenza, Human (complications, virology)
• Lung (immunology, metabolism, pathology, virology)
• Male
• MicroRNAs (genetics)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Prognosis
• Stromal Interaction Molecule 1 (genetics, metabolism)