title: Role of IFN-γ, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps.
abstract: BACKGROUND
  Mucociliary dysfunction is a prominent pathophysiological feature of chronic rhinosinusitis with nasal polyps (CRSwNP); however, the precise mechanisms underlying mucociliary dysfunction are still unclear.
  
  
  OBJECTIVE
  The aim of this study was therefore to evaluate the effects of IFN-γ, IL-13, and IL-17 on human nasal mucociliary differentiation and ciliary beat frequency (CBF) in patients with CRSwNP.
  
  
  METHODS
  Human 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 with10 ng/mL each of IFN-γ, IL-13, or IL-17 for 14 days and assessed for expression of specific morphological markers and factors associated with mucociliary differentiation, the percentage of ciliated and goblet cells, and CBF.
  
  
  RESULTS
  In comparison with control subjects, percentage of ciliated cells and CBF were decreased; while percentage of goblet cells, FOXJ1, and MUC5AC mRNA expression were increased in nasal polyp-derived epithelial cultures. Treatment with IFN-γ and IL-13 significantly decreased the expression of β-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-γ 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.
  
  
  CONCLUSIONS
  The demonstration that IFN-γ 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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.|Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.
authors.forename: N
authors.initials: N
authors.lastname: Meng
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.
authors.forename: E
authors.initials: E
authors.lastname: Fan
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.|Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D015415:Biomarkers; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology*; D009298:Nasal Polyps / Q000150:complications* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012220:Rhinitis / Q000150:complications* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012852:Sinusitis / Q000150:complications* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D018793:Interleukin-13; D020381:Interleukin-17; D012333:RNA, Messenger; D007371:Interferon-gamma
keywords: interferon-γ; interlukin-13; interlukin-17; mucociliary regulation; nasal polyp