MicroRNA-223-3p regulates allergic inflammation by targeting INPP4A

Introduction: Emerging evidence indicates that physiological and pathological conditions of the nose are posttranscriptionally regulated by microRNAs, a class of small noncoding RNAs. Recently, microRNA-223-3p has been increasingly implicated in the modulation of allergic rhinitis Objective: This study aimed to assess the role and mechanism of microRNA-223-3p in a mouse model of allergic rhinitis. Methods: The expression level of miR-223-3p was measured in the serum of 41 allergic rhinitis patients and 39 healthy controls using quantitative real time polymerase chain reaction. BALB/c mice were used to establish an allergic rhinitis model by intraperitoneal sensitization and intranasal challenge with ovalbumin. MicroRNA-223-3p agomir/antagomir was then intranasally administered to mice after ovalbumin challenge for another week. The symptoms of nasal rubbing and sneezing were recorded. Serum ovalbumin-specific immunoglobulin E concentration, microRNA-223-3p expression and proinflammatory cytokine (IL-4, IL-5, IFN-gamma) levels in nasal mucosa were measured by ELISA and quantitative real time polymerase chain reaction, respectively. Histopathologic changes were evaluated using hematoxylin and eosin staining. Results: MicroRNA-223-3p levels increased significantly in both allergic rhinitis patients and allergic rhinitis mice. In addition, upregulation of microRNA-223-3p levels by nasal administration of microRNA-223-3p agomir also markedly increased the concentration of ovalbumin -specific IgE, the frequencies of nasal rubbing and sneezing, the levels of proinflammatory cytokines (IL-4, IL-5, IFN-gamma) and eosinophil infiltration in the nasal mucosa of allergic rhinitis mice. Moreover, microRNA-223-3p antagomir appeared to strongly ameliorate the symptoms and pathology in nasal mucosa. Subsequently, we demonstrated for the first time that microRNA-223-3p negatively regulated INPP4A expression by binding with the 3' untranslated region (3'UTR) of INPP4A. Conclusions: These findings indicate that microRNA-223-3p plays an important role in regulating the pathology and symptoms of allergic rhinitis by targeting INPP4A. (C) 2020 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda.