title: Azelastine enhances the clinical efficacy of glucocorticoid by modulating MKP-1 expression in allergic rhinitis.
abstract: Azelastine was suggested as a supplementary choice of glucocorticoid for the control of moderate to severe allergic rhinitis (AR). However, the underlying mechanism has not been completely understood. In this study, primary cultured nasal epithelial cells and bronchial epithelial cells were stimulated with proinflammatory cytokines (IL-1β and IL-17A) and anti-inflammatory agents (azelastine and budesonide) in vitro. The expression of intercellular adhesion molecule 1 (ICAM-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1) was examined using qPCR and ELISA, respectively. Moreover, the additive effects of azelastine and budesonide nasal spray on nasal ICAM-1 level and total nasal symptom scores were evaluated in six uncontrolled severe AR patients by budesonide nasal spray alone. We found azelastine significantly inhibited cytokine-induced ICAM-1 upregulation, which is reversed by MKP-1 silencing. Azelastine and budesonide additively increased MKP-1 expression and inhibited ICAM-1 expression in vitro. After treatment for two consecutive weeks, combined azelastine and budesonide nasal spray significantly decreased nasal ICAM-1 level and TNSS in six uncontrolled AR patients. Our findings suggested that azelastine is able to additively enhance the anti-inflammatory effect of budesonide by modulating MKP-1 expression, which may implicate in the treatment of uncontrolled severe AR.
authors: Allergy and Cancer Center, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
authors: Xi
authors: X
authors: Luo
authors: Renqiang
authors: R
authors: Ma
authors: Xingmei
authors: X
authors: Wu
authors: Desheng
authors: D
authors: Xian
authors: Jian
authors: J
authors: Li
authors: Zhonglin
authors: Z
authors: Mou
authors: Huabin
authors: H
authors: Li
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001980:Bronchi / Q000473:pathology; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D054638:Dual Specificity Phosphatase 1 / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D059085:Nasal Sprays; D010793:Phthalazines / Q000494:pharmacology*; D065631:Rhinitis, Allergic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D020381:Interleukin-17; D053583:Interleukin-1beta; D059085:Nasal Sprays; D010793:Phthalazines; D018799:Intercellular Adhesion Molecule-1; D019819:Budesonide; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C020976:azelastine