Abstract
Background: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury that has a high mortality rate and leads to substantial healthcare costs. MicroRNA-124-3p (miR-124-3p) helps to suppress inflammation during a pulmonary injury. However, its mechanism of action is largely unknown, and its role in ARDS remains to be determined.Methods: Mice and NR8383 cells were exposed to lipopolysaccharides (LPS) to induce ARDS, and their miR-124-3p levels were determined. After a miRNA agomir was administrated to the mice, their pulmonary injuries were evaluated by H&E staining and assays for peripheral inflammatory cytokine levels. The direct interaction between miR-124-3p and p65 was predicted, and then confirmed by a luciferase activity assay. The role played by miRNA-124-3p in regulating p65 expression was further examined by transfection with its agomir, and its role in cell apoptosis was investigated by observing the effects of miRNA overexpression in vitro and in vivo.Results: After exposure to LPS, there was a consistent decrease in miR-124-3p expression in the lungs of mice and in NR8383 cells. After treatment with the miR-124-3p agomir, the degrees of pulmonary injury (e.g. alveolar hemorrhage and interstitial edema), and the increases in IL-1β, IL-6, and TNF-α levels induced by LPS were significantly attenuated. Overexpression of miR-124-3p in NC8383 cells and lung tissues significantly suppressed LPS-induced p65 expression and cell apoptosis.Conclusions: These results suggest that miR-124-3p directly targeted p65, and thereby decreased the levels of inflammation and pulmonary injury in a mouse model of ARDS.
Highlights
Acute respiratory distress syndrome (ARDS) occurs when fluid builds up in the tiny elastic air sacs in lungs
We examined the levels of miR-124-3p and miR-138-5p in NR8383 cells that had been exposed to LPS, and found that those levels were significantly decreased when compared with the levels in control cells. These findings suggested that those miRNAs might assist in regulating the activity of macrophages, and be associated with ARDS
It is well accepted that NF-κB is closely associated with ARDS because of the important role it plays in managing inflammation; the mechanism by which NF-κB activity is regulated remains largely unknown
Summary
Acute respiratory distress syndrome (ARDS) occurs when fluid builds up in the tiny elastic air sacs (alveoli) in lungs. The fluid prevents the lungs from filling with sufficient quantities of air, which results in less oxygen reaching the bloodstream. Methods: Mice and NR8383 cells were exposed to lipopolysaccharides (LPS) to induce ARDS, and their miR-124-3p levels were determined. Results: After exposure to LPS, there was a consistent decrease in miR-124-3p expression in the lungs of mice and in NR8383 cells. After treatment with the miR-124-3p agomir, the degrees of pulmonary injury (e.g. alveolar hemorrhage and interstitial edema), and the increases in IL-1β, IL-6, and TNF-α levels induced by LPS were significantly attenuated. Overexpression of miR-124-3p in NC8383 cells and lung tissues significantly suppressed LPS-induced p65 expression and cell apoptosis. Conclusions: These results suggest that miR-124-3p directly targeted p65, and thereby decreased the levels of inflammation and pulmonary injury in a mouse model of ARDS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
