Abstract
Mast cells play a central role in asthma. Moreover, serum miRNA-221-3p (miR-221) has been shown to be markedly increased in children with asthma. In the current study, we aimed to examine miR-221 expression in an asthma model and elucidate the mechanisms regulating interleukin (IL)-4 secretion in mast cells. Using polymerase chain reaction, we found that miR-221 was upregulated in a murine asthma model and in P815 mast cells after lipopolysaccharide (LPS) stimulation. Moreover, miR-221 upregulated IL-4 secretion from P815 cells, as shown by enzyme-linked immunosorbent assays. Bioinformatics analysis, luciferase reporter gene assays, and western blotting showed that phosphatase and tensin homolog (PTEN) was a target of miR-221 and could block IL-4 secretion stimulated by miR-221. The phosphorylation of p38 (protein) and activity of nuclear factor-kappaB (NF-κB) were increased after overexpression of miR-221, as shown by electrophoretic mobility shift assays. Finally, treatment with specific inhibitors could block IL-4 secretion. In conclusion, miR-221, which was overexpressed in a murine asthma model, stimulated IL-4 secretion in mast cells through a pathway involving PTEN, p38, and NF-κB.
Highlights
Bronchial asthma is caused by chronic inflammation of the airways involving a variety of cells, including eosinophils, mast cells, and their components
Because miR-221 was found to be increased in pediatric asthmatics [7], reverse transcription (RT)-polymerase chain reaction (PCR) was used to confirm the changes in lung tissues in the murine asthma model
MiR-221 was upregulated in the lungs of model mice, suggesting that miR-221 may play an important role in the onset or development of asthma
Summary
Bronchial asthma is caused by chronic inflammation of the airways involving a variety of cells, including eosinophils, mast cells, and their components. Asthma has the highest morbidity of all childhood chronic respiratory diseases and its prevalence has increased significantly [1]; the pathophysiology of asthma is still not completely clear. Studies have shown that mast cells are critical for the immediate reaction in bronchial asthma [2]. By releasing a large number of inflammatory mediators, mast cells can regulate. MiRNA-221 in Asthmatic Lungs and Mast Cells
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