Interleukin-17A promotes MUC5AC expression and goblet cell hyperplasia in nasal polyps via the Act1-mediated pathway

Wentong Xia; Jing Bai; Xingmei Wu; Yi Wei; Shaoyan Feng; Lei Li; Jia Zhang; Guanxia Xiong; Yunping Fan; Jianbo Shi; Huabin Li

doi:10.1371/journal.pone.0098915

Interleukin-17A promotes MUC5AC expression and goblet cell hyperplasia in nasal polyps via the Act1-mediated pathway

PLoS One. 2014 Jun 3;9(6):e98915. doi: 10.1371/journal.pone.0098915. eCollection 2014.

Authors

Wentong Xia¹, Jing Bai², Xingmei Wu², Yi Wei², Shaoyan Feng³, Lei Li⁴, Jia Zhang², Guanxia Xiong², Yunping Fan³, Jianbo Shi², Huabin Li¹

Affiliations

¹ 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.
² Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
³ Department of Otolaryngology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
⁴ Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

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.

Method: 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).

Conclusion: 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Cell Line
Cluster Analysis
Connexin 43 / metabolism*
Gene Expression Profiling
Gene Expression Regulation* / drug effects
Goblet Cells / metabolism*
Goblet Cells / pathology
Humans
Hyperplasia
Interleukin-17 / metabolism*
Interleukin-17 / pharmacology
MAP Kinase Signaling System
Mucin 5AC / genetics*
Nasal Polyps / genetics*
Nasal Polyps / metabolism*
Peptide Fragments / metabolism*
Signal Transduction*

Substances

ACT1 protein
Connexin 43
Interleukin-17
Mucin 5AC
Peptide Fragments

Grants and funding

This study is supported by National Nature and Science Grant of China (No. 81070772, 81271054) and Program for New Century Excellent Talents in University (No. NCET-10-0851). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.