title: miRNA-221-3p Enhances the Secretion of Interleukin-4 in Mast Cells through the Phosphatase and Tensin Homolog/p38/Nuclear Factor-kappaB Pathway.
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.
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.
authors.forename: Qianyuan
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.
authors.forename: Huan
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.|Department of Pediatrics, Jiangsu Huai'an Maternity and Children's Hospital, Huai'an, Jiangsu, China 223002.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.
authors.forename: Deyu
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China 210008.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D008840:Microfilament Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D000070876:Tensins; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C546122:MIRN221 microRNA, mouse; D035683:MicroRNAs; D008840:Microfilament Proteins; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D000070876:Tensins; D051193:Toll-Like Receptors; D015847:Interleukin-4; D048051:p38 Mitogen-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase