BackgroundMucociliary dysfunction is a prominent pathophysiological feature of chronic rhinosinusitis with nasal polyps (CRSwNP); however, the precise mechanisms underlying mucociliary dysfunction are still unclear. ObjectiveThe aim of this study was therefore to evaluate the effects of IFN-, IL-13, and IL-17 on human nasal mucociliary differentiation and ciliary beat frequency (CBF) in patients with CRSwNP. MethodsHuman nasal epithelial cells from tissue of patients with CRSwNP and control subjects were established as air-liquid interface (ALI) primary cultures. Confluent cultures were incubated with10ng/mL each of IFN-, IL-13, or IL-17 for 14days and assessed for expression of specific morphological markers and factors associated with mucociliary differentiation, the percentage of ciliated and goblet cells, and CBF. ResultsIn comparison with control subjects, percentage of ciliated cells and CBF were decreased; while percentage of goblet cells, FOXJ1, and MUC5ACmRNA expression were increased in nasal polyp-derived epithelial cultures. Treatment with IFN- and IL-13 significantly decreased the expression of -tubulin IV (specific cilia marker), ciliated cell number, and expression of FOXJ1 and DNAI2, in epithelial cultures derived from both CRSwNP patients and control subjects. Furthermore, while both IFN- and IL-13 treatment significantly decreased the CBF of cells from both CRSwNP patients and control subjects, IL-13 additionally significantly increased goblet cell number and the expression of MUC5AC and CLCA1, in these cultures. IL-17 treatment did not significantly affect ciliated or goblet cell differentiation, CBF, nor MUC5AC and CLCA1 expression, but increased both MUC5B mRNA and protein expression in these cultures. Conclusion and clinical relevanceThe demonstration that IFN- and IL-13 both significantly reduce ciliated cell differentiation and CBF in CRSwNP patients, and IL-13 additionally induces significant goblet cell hyperplasia and MUC5AC mucin expression, as well as IL-17 significantly increases MUC5B mucin expression, suggests that these inflammatory cytokines may be potential therapeutic targets in the management of CRSwNP.
基金：
Program for Changjiang Scholars and Innovative Research TeamProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT13082]; 12th five-year science and technology support project [2014BAI07B04]; National Science Fund for the Major International Joint Research Program [81420108009]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81100704, 81441029, 81441031]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7131006]; Ministry of Health Foundation [201202005]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201310]; Capital Health Research and Development of Special [2011-1017-06]; Specialized Research Fund for the Doctoral Program of Higher Education of ChinaSpecialized Research Fund for the Doctoral Program of Higher Education (SRFDP) [20111107120004]; Special Fund of Sanitation Elite Reconstruction of Beijing [2009-2-007]; Beijing Health Bureau Program for high level talents [2009-2-007, 2011-3-043, 2014-3-018]; Program for Changjiang Scholars and Innovative Research TeamProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT13082]; 12th five-year science and technology support project [2014BAI07B04]; National Science Fund for the Major International Joint Research Program [81420108009]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81100704, 81441029, 81441031]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7131006]; Ministry of Health Foundation [201202005]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201310]; Capital Health Research and Development of Special [2011-1017-06]; Specialized Research Fund for the Doctoral Program of Higher Education of ChinaSpecialized Research Fund for the Doctoral Program of Higher Education (SRFDP) [20111107120004]; Special Fund of Sanitation Elite Reconstruction of Beijing [2009-2-007]; Beijing Health Bureau Program for high level talents [2009-2-007, 2011-3-043, 2014-3-018]
第一作者机构：[1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China[2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, 17 HouGouHuTong, Beijing 100005, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China[2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, 17 HouGouHuTong, Beijing 100005, Peoples R China[3]Capital Med Univ, Beijing TongRen Hosp, Dept Allergy, Beijing, Peoples R China[*1]Beijing Inst Otolaryngol, 17 HouGouHuTong, Beijing 100005, Peoples R China
推荐引用方式(GB/T 7714)：
Jiao J.,Duan S.,Meng N.,et al.Role of IFN-, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps[J].CLINICAL AND EXPERIMENTAL ALLERGY.2016,46(3):449-460.doi:10.1111/cea.12644.
APA：
Jiao, J.,Duan, S.,Meng, N.,Li, Y.,Fan, E.&Zhang, L..(2016).Role of IFN-, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps.CLINICAL AND EXPERIMENTAL ALLERGY,46,(3)
MLA：
Jiao, J.,et al."Role of IFN-, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps".CLINICAL AND EXPERIMENTAL ALLERGY 46..3(2016):449-460
