Abstract
The importance of understanding how interleukin-33 (IL-33) is regulated (particularly by miRs) is critical in IL-33 biology, and evidence of this in asthma pathology is limited. MicroRNA profiling of cells isolated from bronchoalveolar lavage of 14 asthmatic patients and 11 healthy controls revealed miR-200b and miR-200c were significantly reduced in asthmatic patients compared with healthy controls. The reduction was validated in two independent models of allergen-induced allergic airway inflammation and further demonstrated to be inversely correlated with asthma severity, as well as increased IL-33 production in asthmatic patients. In addition, the miR-200b and miR-200c binding sites in the 3' UTR of IL-33 mRNA were identified by bioinformatics analysis and reporter gene assay. More importantly, introduction of miR-200b and miR-200c reduced, while inhibition of endogenous miR-200b and miR-200c increased, the induction of IL-33 expression in lung epithelial cells. Exogenous administration of miR-200b to lungs of mice with allergic inflammation resulted in a decrease in IL-33 levels and resolution of airway inflammation phenotype. In conclusion, miR-200b and miR-200c by regulating the expression of IL-33 have a role in bronchial asthma, and dysregulation of expression of miR-200b/c may be the underlying mechanism resulting in the asthmatic phenotype.