1066 Antagonism of microRNA-21 suppressed the airway inflammation in a mouse model of bronchial asthma

Wednesday, 14 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Hwa Young Lee , Seoul St.Mary's Hospital, Seoul, South Korea

In Kyoung Kim, PhD , Seoul St.Mary's Hospital, Seoul, South Korea

Joon Young Choi , Seoul St.Mary's Hospital, Seoul, South Korea

Hea Yon Lee , St. Mary's Hospital, Seoul, South Korea

Sei Won Kim , Seoul St.Mary's Hospital, Seoul, South Korea

Chin Kook Rhee, MD , Seoul St.Mary's Hospital, Seoul, South Korea

Young Kyoon Kim, MD , Seoul St.Mary's Hospital, Seoul, South Korea

Soon Seog Kwon, MD & PhD , Pucheon St.Mary's Hospital, Seoul, South Korea

Sook Young Lee , Seoul St.Mary's Hospital, Seoul, South Korea

Background : In previous reports, microRNA-21 (miR-21) was upregulated in allergic airway inflammation mediating Th2 immune response [1,2]. This study was designed to investigate the effect of miR-21 antagonism on mouse model of acute bronchial asthma.

Methods : BALB/c mice were sensitized and challenged with ovalbumin (OVA). Anti-miR-21 antagomir and control scrambled RNA was daily injected by intranasal inhalation from the day of sensitization 5 times a week.  Changes of cell counts, Th2 cytokines in bronchoalveolar (BAL) fluid and airway hyperresponsiveness (AHR) were evaluated. Histopathologic changes and expression of miR-21 were compared in lung tissues between antagomir treatment group and control groups.     

Results : Treatment of anti-miR-21 antagomir suppressed AHR compared with OVA challenged group and scrambled RNA treatment group. Antagomir treatment reduced total cell counts and eosinophil counts in BAL fluid. Th2 cytokines such as IL-4, IL-5 and IL-13 were significantly decreased in BAL fluid of anti-miR-21 antagomir treatment group.

Conclusions : Antagonism of miR-21 by antagomir inhalation had suppressive effects on development of allergic airway inflammation in acute bronchial asthma model. These results suggest that miR-21 antagomir could be a potential target agent for the treatment of bronchial asthma.

References)

1)         Lu TX, Munitz A, Rothenberg ME. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. Journal of immunology 2009;182:4994-5002.

2)         Lu TX, Hartner J, Lim EJ, Fabry V, Mingler MK, Cole ET, et al. MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. Journal of immunology 2011;187:3362-73.