EphA2 receptor and its ephrin ligands are involved in virus infection, epithelial permeability, and chemokine secretion. We hypothesized that ephrinA1/ephA2 signaling participates in rhinovirus (RV)-induced antiviral immune response in sinonasal mucosa of patients with chronic rhinosinusitis (CRS). Therefore, we investigated the expression of ephrinA1/ephA2 in normal and inflamed sinonasal mucosa and evaluated whether they regulate chemokine secretion and the production of antiviral immune mediators including interferons (IFNs) in RV-infected human primary sinonasal epithelial cells. For this purpose, the expression and distribution of ephrinA1/ephA2 in sinonasal mucosa were evaluated with RT-qPCR, immunofluorescence, and western blot. Their roles in chemokine secretion and the production of antiviral immune mediators such as type I and III IFNs, and interferon stimulated genes were evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to RV and poly(I:C). We found that ephrinA1/ephA2 were expressed in normal mucosa and their levels increased in inflamed sinonasal mucosa of CRS patients. RV infection or poly(I:C) treatment induced chemokine secretion which were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. The production of antiviral immune mediators enhanced by rhinovirus or poly (I:C) is increased by blocking ephA2 compared with that of cells stimulated by either rhinovirus or poly(I:C) alone. In addition, blocking ephA2 attenuated RV replication in cultured cells. Taken together, these results describe a novel role of ephrinA1/ephA2 signaling in antiviral innate immune response in sinonasal epithelium, suggesting their participation in RV-induced development and exacerbations of CRS.

Background and Objectives: Vitamin D modulates immunity, including that of allergic diseases, and plays its roles through contact with vitamin D receptors (VDR). Recent studies have shown that patients with allergic rhinitis have low systemic serum vitamin D level. However, the expression of VDR in local tissue such as human nasal mucosa has not been investigated. Our study demonstrated that, in nasal mucosa of normal controls and patients with allergic rhinitis. Materials and Method: Nasal mucosa were harvested from twenty-five patients who had normal nasal mucosa and twentyfive patients with allergic rhinitis. After the total RNA isolation, we performed RT-PCR, immunohistochemical staining and western blot analysis. Results: VDR were expressed in submucosal glands and the superficial layer of epithelial cell, and that inflammatory cells are expressed more highly in the nasal mucosa of patients with allergic rhinitis compared to those without. In the mucosa of patients with allergic rhinitis, VDR expression level was upregulated compared to that in normal nasal mucosa. Conclusion:This findings suggest that VDR plays a role in the pathogenesis of allergic rhinitis. Additional research is needed to determine the mechanism and consequences of VDR upregulation.