Inhibition of MicroRNA-21 by an antagomir ameliorates allergic inflammation in a mouse model of asthma.

Aim of the Study: MicroRNA-21 (miR-21) is up-regulated during allergic airway inflammation, reflecting a Th2 immune response. We investigated the effects of an miR-21 antagomir and its mechanism of action in a mouse model of acute bronchial asthma. Materials and Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA). The anti-miR-21 antagomir was administered by intranasal inhalation from the day of sensitization. Changes in cell counts, Th2 cytokine levels in bronchoalveolar (BAL) fluid, and airway hyper-responsiveness (AHR) were examined. Histopathological changes and expression levels of miR-21 in lung tissues were analyzed. The mechanism of action of the antagomir was investigated by counting CD4(+)/CD8(-) T cells in splenocytes and by measuring the expression levels of transcription factors associated with T cell polarization. Results: MiR-21 expression was selectively down-regulated in the lung tissues of mice treated with anti-miR-21. The antagomir suppressed AHR compared with that of the OVA-challenged and scrambled RNA-treated groups. It also reduced the total cell and eosinophil counts in BAL fluid and the levels of Th2 cytokines, including IL-4, IL-5, and IL-13. The direct target of miR-21, IL-12p35, was induced in the antagomir-treated group, decreasing the CD4(+)/CD8(-) T cell proportions in splenocytes. The levels of transcription factors involved in the Th2-signaling pathway were reduced in lung tissues on treatment with the antagomir. Conclusions: The miR-21 antagomir suppresses the development of allergic airway inflammation in a mouse model of acute bronchial asthma, inhibiting Th2 activation. These results suggest that this antagomir might be useful for treating bronchial asthma.