Abstract
Background
Asthma 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).
Methods
In 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.
Results
We 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.
Conclusions
These 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.