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

Xia W, Bai J, Wu X, Wei Y, Feng S, Li L, Zhang J, Xiong G, Fan Y, Shi J, Li H - PLoS ONE (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

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.

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.

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DNA microarray analysis of PECs stimulated by IL-17A.Shown are the heatmap of genes upregulated in stimulated PECs (A) and the scatter-plot for stimulated vs unstimulated PECs (B).
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pone-0098915-g003: DNA microarray analysis of PECs stimulated by IL-17A.Shown are the heatmap of genes upregulated in stimulated PECs (A) and the scatter-plot for stimulated vs unstimulated PECs (B).

Mentions: To assess the regulatory effect of IL-17A on gene expression in nasal epithelial cells in vitro, we then screened the upregulated gene expression in cultured PECs by DNA microarray analysis after IL-17A stimulation (10 ng/mL) for 24 h. As a result, we identified 46 upregulated related genes (Fig 3). Of these genes, MUC5AC was increased 6.25 fold in stimulated PECs, and act1 was increased 4 fold in PECs. To further validate the promotive effect of IL-17A on MUC5AC expression and the underlying pathways, we examined IL-17RA, IL-17RC, act1 and MUC5AC mRNA expression after IL-17A stimulation. As shown in Fig. 4, IL-17A significantly increased IL-17RA, IL-17RC, act1 and MUC5AC mRNA expression in cultured PECs in a dose-dependent manner (p<0.05). Accordingly, MUC5AC protein level was dose-dependently upregulated in cultured PECs in the presence of IL-17A as well (p<0.05).


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

Xia W, Bai J, Wu X, Wei Y, Feng S, Li L, Zhang J, Xiong G, Fan Y, Shi J, Li H - PLoS ONE (2014)

DNA microarray analysis of PECs stimulated by IL-17A.Shown are the heatmap of genes upregulated in stimulated PECs (A) and the scatter-plot for stimulated vs unstimulated PECs (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043856&req=5

pone-0098915-g003: DNA microarray analysis of PECs stimulated by IL-17A.Shown are the heatmap of genes upregulated in stimulated PECs (A) and the scatter-plot for stimulated vs unstimulated PECs (B).
Mentions: To assess the regulatory effect of IL-17A on gene expression in nasal epithelial cells in vitro, we then screened the upregulated gene expression in cultured PECs by DNA microarray analysis after IL-17A stimulation (10 ng/mL) for 24 h. As a result, we identified 46 upregulated related genes (Fig 3). Of these genes, MUC5AC was increased 6.25 fold in stimulated PECs, and act1 was increased 4 fold in PECs. To further validate the promotive effect of IL-17A on MUC5AC expression and the underlying pathways, we examined IL-17RA, IL-17RC, act1 and MUC5AC mRNA expression after IL-17A stimulation. As shown in Fig. 4, IL-17A significantly increased IL-17RA, IL-17RC, act1 and MUC5AC mRNA expression in cultured PECs in a dose-dependent manner (p<0.05). Accordingly, MUC5AC protein level was dose-dependently upregulated in cultured PECs in the presence of IL-17A as well (p<0.05).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus