Down-regulation of miR-155 inhibits inflammatory response in human pulmonary microvascular endothelial cells infected with influenza A virus by targeting sphingosine-1-phosphate receptor 1

作     者：Si-Mei Shen Hao Jiang Jiang-Nan Zhao Yi Shi Shen Si-Mei;Jiang Hao;Zhao Jiang-Nan;Shi Yi

作者机构：Department of Respiratory and Critical Care MedicineJinling HospitalMedical School of Nanjing UniversityNanjingJiangsu 210016China Department of Emergency MedicineThe Second Affiliated HospitalSoutheast UniversityNanjingJiangsu 210003China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2020年第133卷第20期

页      面：2429-2436页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：a grant from the National Nature Science Foundation of China(No.81470206). 

主　　题：MicroRNA-155 Sphingosine 1-phosphate receptor 1 Influenza A virus Endothelial cells 

摘      要：Background:Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells.Methods:Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis.Results:MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs. Conclusion:MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.