Hypoxia regulates IL-17A secretion from nasal polyp epithelial cells

// Qian Xiu 1 , Chenfei Kong 2 , Yiyao Gao 2 , Yang Gao 3 , Jichao Sha 1 , Na Cui 1 and Dongdong Zhu 1 1 Department of Otolaryngology-Head and Neck Surgery, China-Japan Union Hospital, Jilin University, Changchun, China 2 Department of Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun, China 3 Department of Clinical Medicine, Bethune Medical College, Jilin University, Changchun, China Correspondence to: Dongdong Zhu, email: zhudd@jlu.edu.cn Keywords: chronic rhinosinusitis with nasal polyps; hypoxia; epithelial cells; hypoxia inducible factors; interleukin 17A Received: March 31, 2017 Accepted: September 05, 2017 Published: October 31, 2017 ABSTRACT Hypoxia creates a microenvironment conducive to polypogenesis by regulating immune responses of the nasal polyp (NP) epithelium. We explored the immunocompetence of NP and control epithelial cells in response to hypoxia, to investigate potential relationships with polypogenesis. Three groups of tissue samples were collected: inferior turbinate (IT)and NP from individuals with chronic rhinosinusitis with NPs (CRSwNP), and control IT. A positive relationship was detected between HIF1α, HIF2α protein expression in epithelial cells and endoscope score in NP samples, while there was a negative correlation between HIF1α expression and degree of eosinophil infiltration. Epithelial IL-17A expression was lower in NPs than in IT samples from either controls or patients with CRSwNP. Primary human nasal epithelial cells were cultured under hypoxic or normoxic conditions. Enzyme-linked immunosorbent assays demonstrated decreased IL-17A expression upon prolonged exposure to hypoxia in both IT and NP samples from patients with CRSwNP, while IL-17A increased in control IT epithelial cells; correlation and time-dependency were observed between HIF1α and IL-17A expression in both IT and NP samples from patients with CRSwNP. These observations suggest that hypoxia is involved in the pathogenesis of NPs through regulation of IL-17A secretion and HIF1α and HIF2α expression in the NP epithelium.