Monday, 5 December 2011: 13:15 - 13:30
Gran Cancún 3 (Cancún Center)
Jia-Wang Wang, PhD
,
Internal Medicine, University of South Florida, Tampa, FL
Kunyu Li, BS
,
Internal Medicine, University of South Florida, Tampa, FL
Gary Hellermann, PhD
,
Internal Medicine, University of South Florida, Tampa, FL
Richard F. Lockey, MD
,
Division of Allergy & Immunology, University of South Florida and James A. Haley Veterans' Hospital, Tampa, FL
Subhra Mohapatra, PhD
,
Nanomedicine Research Center and Divison of Translational Medicine, Depts of Molecular Medicine and Internal Medicine , University of South Florida and James V Haley Veterans' Hospital , Tampa, FL
Shyam Mohapatra, PhD
,
USF Nanomedicine Research Center, University of South Florida College of Medicine & VA Hospital, Tampa, FL
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 down-regulated 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 down-regulating critical genes such as Akt, Elk1 and Cbl1. miR-150 may be an attractive candidate for asthma gene therapy.
