Increased Expression of Importin α3 (KPNA4) and Decreased VDR in the Lung of OVA-Sensitized and Challenged Mice

Abstract

Rationale: The nuclear import of p65 and p50 subunits of activated NF-кB is dependent on importin α3 (KPNA4) and importin α4 (KPNA3). We previously reported that pro-inflammatory cytokines increase the expression of importin α3 and decrease the expression of VDR in Human bronchial smooth muscle cells (HBSMCs). Our results also demonstrate that co- stimulation with calcitriol attenuated the increased expression of importin α3 thereby leading to decrease in the activated NF-κB in the nucleus through a mechanism mediated by VDR. In this study, we evaluated the mRNA and protein expression of VDR and importin α3 in the lungs of OVA-sensitized and challenged mice as compared to control mice. Methods: BALB/c mice were sensitized and challenged with OVA and AHR to methacholine was established. Protein and mRNA expressions of VDR, and importin α3 in whole lung tissue were analyzed using immunofluorescence and qPCR, respectively. Results: There was significantly higher mRNA and protein expression of importin α3 and decreased expression of VDR in the lung tissue of OVA-sensitized and challenged mice as compared to PBS mice. Conclusions: The decrease in the expression of VDR in OVA sensitized mice suggest the role of vitamin D in allergic asthma. An increase in importin α3 is likely due to a decrease in VDR expression in lungs of OVA-sensitized mice. We, therefore, conclude that Vitamin D supplementation in asthmatic mice can decrease the AHR and the expression of importin α3 and thus inflammation. Thus, Vitamin D might be helpful in alleviating allergic airway inflammation and airway hyperresponsiveness in allergic asthma.