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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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Expression of IL-17A, MUC5AC and act1 in polyp tissues and normal controls.(A–C) The mRNA levels of IL-17A, MUC5AC and act1 in polyp tissues and normal controls. (D) The association of IL-17A and MUC5AC mRNA in polyp tissues. (E) The association of IL-17A and act1 mRNA in polyp tissues. (F) The protein levels of act1 in polyp tissues and normal controls. (G) Representative western blot results of act1 in polyp tissues and normal controls are shown. (H) Densitometric analysis of act1 in polyp tissues and normal controls. The data are expressed as the medians (IQRs).
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pone-0098915-g002: Expression of IL-17A, MUC5AC and act1 in polyp tissues and normal controls.(A–C) The mRNA levels of IL-17A, MUC5AC and act1 in polyp tissues and normal controls. (D) The association of IL-17A and MUC5AC mRNA in polyp tissues. (E) The association of IL-17A and act1 mRNA in polyp tissues. (F) The protein levels of act1 in polyp tissues and normal controls. (G) Representative western blot results of act1 in polyp tissues and normal controls are shown. (H) Densitometric analysis of act1 in polyp tissues and normal controls. The data are expressed as the medians (IQRs).

Mentions: We next examined the gene expression levels of IL-17A, MUC5AC and act1 in polyp tissues and normal controls. The mRNA level of IL-17A was 3.3[2.0, 5.5] in polyp tissues and 0.8[0.4, 1.2] in normal controls, and the mRNA level of MUC5AC was 4.4[2.3, 6.3] in polyp tissues and 1.2[0.4, 2.2] in normal controls. In accordance with the histological staining, the mRNA levels of IL-17A and MUC5AC were significantly increased in polyp tissues compared with the normal controls (Fig. 2A and B, p<0.05). There was significant association of IL-17A and MUC5AC mRNA in polyp tissues (Fig. 2D, p<0.05). Moreover, there was significant difference in act1 mRNA in polyp tissues (1.1[0.7, 1.8]) and normal controls (0.8[0.3, 1.2])(Fig 2C, p<0.05), and act1 mRNA was significantly correlated with IL-17A mRNA in polyp tissues (Fig 2E, 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)

Expression of IL-17A, MUC5AC and act1 in polyp tissues and normal controls.(A–C) The mRNA levels of IL-17A, MUC5AC and act1 in polyp tissues and normal controls. (D) The association of IL-17A and MUC5AC mRNA in polyp tissues. (E) The association of IL-17A and act1 mRNA in polyp tissues. (F) The protein levels of act1 in polyp tissues and normal controls. (G) Representative western blot results of act1 in polyp tissues and normal controls are shown. (H) Densitometric analysis of act1 in polyp tissues and normal controls. The data are expressed as the medians (IQRs).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098915-g002: Expression of IL-17A, MUC5AC and act1 in polyp tissues and normal controls.(A–C) The mRNA levels of IL-17A, MUC5AC and act1 in polyp tissues and normal controls. (D) The association of IL-17A and MUC5AC mRNA in polyp tissues. (E) The association of IL-17A and act1 mRNA in polyp tissues. (F) The protein levels of act1 in polyp tissues and normal controls. (G) Representative western blot results of act1 in polyp tissues and normal controls are shown. (H) Densitometric analysis of act1 in polyp tissues and normal controls. The data are expressed as the medians (IQRs).
Mentions: We next examined the gene expression levels of IL-17A, MUC5AC and act1 in polyp tissues and normal controls. The mRNA level of IL-17A was 3.3[2.0, 5.5] in polyp tissues and 0.8[0.4, 1.2] in normal controls, and the mRNA level of MUC5AC was 4.4[2.3, 6.3] in polyp tissues and 1.2[0.4, 2.2] in normal controls. In accordance with the histological staining, the mRNA levels of IL-17A and MUC5AC were significantly increased in polyp tissues compared with the normal controls (Fig. 2A and B, p<0.05). There was significant association of IL-17A and MUC5AC mRNA in polyp tissues (Fig. 2D, p<0.05). Moreover, there was significant difference in act1 mRNA in polyp tissues (1.1[0.7, 1.8]) and normal controls (0.8[0.3, 1.2])(Fig 2C, p<0.05), and act1 mRNA was significantly correlated with IL-17A mRNA in polyp tissues (Fig 2E, 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