EFFECT AND UNDERLYING MECHANISMS OF INTERLEUKIN-13 (IL-13) ON THE BIOLOGICAL FUNCTIONS OF NASAL EPITHELIUM

Abstract

IL-13 is a key Th2 cytokine that acts as an important mediator in airway inflammation and remodeling. However, previous studies do not fully address the question on IL-13 initiation of airway inflammation and remodeling in nasal mucosa. In order to explore the role of IL-13 in upper airway, we use primary hNECs derived from hNESPCs, forming pseudo stratified layers in ALI culture. The hNECs model largely mimics the nasal epithelium in vivo. Our data demonstrate that IL-13 affects ciliated cells via the inhibition of ciliogenesis associated maker FOXJ1’s expression and interference on CP110 translocation. IL-13Rα2 has an important role in IL-13 induced mucus overproduction by upregulating MUC5AC expression and mucociliary dysfunctions through the activation of ERK1/2. IL-13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP. More importantly, IL-13 receptors and ERK1/2 pathways are attractive targets for therapeutic intervention in airway inflammatory disease.