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.
10.1097/CM9.0000000000001036
- Author:
Si-Mei SHEN
1
;
Hao JIANG
2
;
Jiang-Nan ZHAO
1
;
Yi SHI
1
Author Information
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.
- Publication Type:Journal Article
- MeSH:
Down-Regulation;
Endothelial Cells;
Humans;
Influenza A Virus, H1N1 Subtype/genetics*;
Influenza A virus;
Influenza, Human/genetics*;
MicroRNAs/genetics*;
Sphingosine-1-Phosphate Receptors
- From:
Chinese Medical Journal
2020;133(20):2429-2436
- CountryChina
- Language:English
-
Abstract:
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.
