26 MIR-150 Suppresses Lung Inflammation in a Mouse Model of Experimental Asthma

Abstract

BackgroundAsthma is a complex disorder of the immune system caused by a combination of genetic predisposition with environmental exposures. The environmental factors play a predominant role in the etiology of asthma. It is hypothesized that epigenetic changes in miRNAs play a critical role in pathogenesis of asthma as an interface between genetic makeup and environmental exposures. (Wang, Jia-wang; Li, Kunyu; Hellermann, Gary; Lockey, Richard F.; Mohapatra, Subhra; and Mohapatra, Shyam. Regulating the Regulators: microRNA and Asthma. World Allergy Organization Journal. June 2011, Volume 4, Issue 6).MethodsIn the present study, we used miRNA array profiling in a mouse model of ovalbumin-induced asthma to identify differentially regulated miRNAs and characterized miR-150 in terms of cellular and humoral involvement and analysis of lung inflammation markers.ResultsWe found that miR-150 was downregulated in CD4 T lymphocytes during asthmatic inflammation and Th1 and Th2 induction. Over-expression of miR-150 delivered by chitosan nanoparticles inhibited lung inflammation and decreased Th1 and Th2 cytokine levels. miR-150 suppressed Akt3, Cbl1 and Elk1 oncogenes, which are involved in inflammation and cytokine production. Transgenic mice overexpressing miR-150 are resistant to asthma induction, demonstrated by reduced AHR and cytokine inflammation production.ConclusionsThese results suggest that deregulation of miRNAs may be involved in the pathogenesis of asthma and miR-150 may suppress inflammation in asthma by inhibiting cytokine production by downregulating critical genes such as Akt, Elk1 and Cbl1. miR-150 may be an attractive candidate for asthma gene therapy.