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 

机构地区：[1]Department of Respiratory and Critical Care Medicine,Jinling Hospital,Medical School of Nanjing University,Nanjing,Jiangsu 210016,China [2]Department of Emergency Medicine,The Second Affiliated Hospital,Southeast University,Nanjing,Jiangsu 210003,China

出　　处：《Chinese Medical Journal》2020年第20期2429-2436,共8页中华医学杂志（英文版）

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

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.

关 键 词：MicroRNA-155 Sphingosine 1-phosphate receptor 1 Influenza A virus Endothelial cells 

分 类 号：R511.7[医药卫生—内科学]