Intranasal Administration Of Lentiviral MiR-135a Treats Murine Allergic Rhinitis And Its Mechanisms

Objective:To investigate the effect of intranasal administration of lentiviral (Lv) microRNA-135a (miR-135a) in the mice model of allergic rhinitis (AR).Methods:BALB/c mice were sensitized with ovalbumin (OVA) into AR model, the saline as control group. Using intranasal administration system, Lv miR-135a was applied into AR mice. Total serum IgE was determined by enzyme-linked immunosorbent assay (ELISA). The expression of miR-135a and mRNA of transcription factors (GATA binding protein3, GATA-3 and T-box expressed in T cells, T-bet) was quantified by real-time quantitative polymerase chain reaction (RT-qPCR). The change of T-helper (Th) cell polarization was analyszed by flow cytometric analysis. The influx of eosinophils and mast cells in nasal mucosa were detected by hematoxylin and eosin (H&E) and mast cells staining, while observed the lung tissue. Laser scanning confocal microscopy was used to visualize the localization of Lv miR-135a in mast cells. Analysed the expression of miR-135a in bone marrow mast cells (BMMCs) from normal mice and AR mice.Results:Compare to the normal mice, the level of total IgE in the serum was significantly upregulated in the AR mice, however, the level of total IgE in AR mice treated with Lv miR-135a was similar to the normal mice. Intranasal administration of Lv miR-135a downregulated the expression level of GATA-3 mRNA,while upregulated the expression level of miR-135a and T-bet mRNA. Treatment with Lv miR-135a not only appeared to correct the Th cells polarization back to the normal physiological levels, but also strongly suppressed the infiltration of inflammation cells in the nasal mucosa. Lung tissuse had no significantly changed in all the mice. It was observed the Lv miR-135a can be expressed in mast cells in laser scanning confocal microscopy. The expression level of miR-135a was lower in BMMCs from the AR mice than that from the normal mice.Conclusion:Intransal administration of Lv miR-135a can suppress the allergen-induced inflammation safely and effectively, providing the experimental reference and the theoretical basis for lentiviral mediated microRNA treat allergic rhinitis. It is likely that Lv miR-135a mediated changes via direct targeting of GATA-3 in AR mice, and effect the mast cells activation.