title: Interleukin-17A promotes MUC5AC expression and goblet cell hyperplasia in nasal polyps via the Act1-mediated pathway.
abstract: BACKGROUND
  Recent studies demonstrated that nasal polyps (NP) patients in China and other Asian regions possessed distinct Th17-dominant inflammation and enhanced tissue remodeling. However, the mechanism underlying these observations is not fully understood. This study sought to evaluate the association of interleukin (IL)-17A with MUC5AC expression and goblet cell hyperplasia in Chinese NP patients and to characterize the signaling pathway underlying IL-17A-induced MUC5AC expression in vitro.
  
  
  METHODS
  We enrolled 25 NP patients and 22 normal controls and examined the expression of IL-17A, MUC5AC and act1 in polyp tissues by immunohistochemical (IHC) staining, quantitative polymerase chain reaction (qPCR) and western blot. Moreover, by using an in vitro culture system of polyp epithelial cells (PECs), IL-17A-induced gene expression was screened in cultured PECs by DNA microarray. The expression of IL-17RA, IL-17RC, act1 and MUC5AC and the activation of the MAPK pathway (ERK, p38 and JNK), were further examined in cultured PECs and NCI-H292 cells by qPCR and western blotting, respectively.
  
  
  RESULTS
  We found that increased IL-17A production was significantly correlated with MUC5AC and act1 expression and goblet cell hyperplasia in polyp tissues (p<0.05). IL-17A significantly stimulated the expression of IL-17RA, IL-17RC, act1 and MUC5AC, and the activation of the MAPK pathway in cultured PECs and NCI-H292 cells (p<0.05). In addition, IL-17RA, IL-17RC and act1 siRNA significantly blocked IL-17A-induced MUC5AC production in vitro (p<0.05).
  
  
  CONCLUSIONS
  Our results suggest that IL-17A plays a crucial role in stimulating the production of MUC5AC and goblet cell hyperplasia through the act1-mediated signaling pathway and may suggest a promising strategy for the management of Th17-dominant NP patients.
authors.affiliation: Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wentong
authors.initials: W
authors.lastname: Xia
authors.affiliation: Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.affiliation: Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xingmei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Otolaryngology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Guanxia
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Otolaryngology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Shi
authors.affiliation: Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Huabin
authors.initials: H
authors.lastname: Li
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D016000:Cluster Analysis; D018031:Connexin 43 / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D020397:Goblet Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D020381:Interleukin-17 / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D055271:Mucin 5AC / Q000235:genetics*; D009298:Nasal Polyps / Q000235:genetics* / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C541130:ACT1 protein; D018031:Connexin 43; D020381:Interleukin-17; D055271:Mucin 5AC; D010446:Peptide Fragments