miRNA-221-3p Enhances the Secretion of Interleukin-4 in Mast Cells through the Phosphatase and Tensin Homolog/p38/Nuclear Factor-kappaB Pathway

PloS One
Yao ZhouFeng Liu

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.

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Citations

Dec 17, 2016·Cancer Biomarkers : Section a of Disease Markers·Fan ChenShun-E Yang
Dec 1, 2017·Genes·Beata NarożnaAleksandra Szczepankiewicz
Jul 5, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heedoo LeeYang Jin
May 18, 2019·Journal of Cellular Physiology·Seyed Reza MousaviJafar Salimian
May 30, 2019·Archivum Immunologiae Et Therapiae Experimentalis·Krzysztof Specjalski, Ewa Jassem
Aug 18, 2018·Experimental and Therapeutic Medicine·Zhiyong YiGuanlan Liu
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Mar 10, 2021·Clinical and Experimental Medicine·Simone MarcellaStefania Loffredo

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Methods Mentioned

BETA
bronchoalveolar lavage
transfection
Assay
enzyme-linked immunosorbent assays
Protein Assay
electrophoresis
chip

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