Conditioned medium from the bone marrow mesenchymal stem cells modulates immune response via signal transduction and activator of transcription 6 signaling pathway in an allergic rhinitis mouse model

Abstract

Background: Allergic rhinitis (AR) is a common immune disease of the nasal mucosa characterized with immunoglobulin E (IgE)-mediated allergic inflammation after exposure to allergens in susceptible population. Previous reports have demonstrated that the bone marrow mesenchymal stem cells (BMSCs) could reduce allergic inflammation. However, there is little knowledge about whether the culture supernatant of BMSCs (conditioned medium, CM) has similar anti- inflammatory potential in treating AR. Objective: The study aimed to evaluate the immunoregulatory effects of conditioned medium derived from BMSCs (BMSC-CM) on allergic inflammation in an AR mouse model. Material and Methods: The AR murine model was induced by repeated sensitization and challenges with ovalbumin (OVA). Subsequently the allergic symptoms of AR mice, cytokine levels, the histopathological features of the nasal mucosa and T helper 1 (Th1) : T helper 2 (Th2) cells ratio were evaluated. Results: Treatment with BMSC-CM was found as effective as BMSCs in reducing allergic symptoms and inhibiting eosinophilic infiltration in the nasal mucosa. After BMSC-CM or BMSCs administration, the OVA-specific IgE and interleukin 4 levels in serum decreased and interferon gamma level increased compared with AR mice treated with uncultured fresh medium. Flow cytometry analysis revealed a decrease in Th1:Th2 cells ratio after OVA-sensitization and the ratio was reversed by BMSC-CM and BMSCs treatments. Furthermore, the data revealed that BMSC-CM suppressed the production of signal transduction and activator of transcription 6 (STAT6) at messenger RNA and protein levels in the nasal mucosa. Conclusion: BMSC-CM could ameliorate allergic inflammation and regulate the balance of Th cells, and the underlying mechanism was closely related to STAT6 signaling pathway. The immunoregulatory effects of BMSCs could be achieved through paracrine function, and nasal dripping of BMSC-CM might be a novel approach for the treatment of AR.