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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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PAS staining and immunostaining of IL-17A and MUC5AC in polyp tissues and normal controls.(A) Representative results of PAS staining and IHC staining of MUC5AC and IL-17A in polyp tissues and normal controls are shown (magnification, 200×). (B) The mean number of IL-17+ cells in polyp tissues and normal controls. (C) The PAS staining index in polyp tissues and normal controls. (D) The MUC5AC staining score in polyp tissues and normal controls. (E) The association between IL-17A and the PAS staining index in polyp tissues. (F) The association between IL-17A and MUC5AC staining scores in polyp tissues. Data are expressed as the medians (IQRs).
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pone-0098915-g001: PAS staining and immunostaining of IL-17A and MUC5AC in polyp tissues and normal controls.(A) Representative results of PAS staining and IHC staining of MUC5AC and IL-17A in polyp tissues and normal controls are shown (magnification, 200×). (B) The mean number of IL-17+ cells in polyp tissues and normal controls. (C) The PAS staining index in polyp tissues and normal controls. (D) The MUC5AC staining score in polyp tissues and normal controls. (E) The association between IL-17A and the PAS staining index in polyp tissues. (F) The association between IL-17A and MUC5AC staining scores in polyp tissues. Data are expressed as the medians (IQRs).

Mentions: Because IL-17A has been proposed to be significantly upregulated in nasal polyps, we firstly examined the expression of IL-17A and MUC5AC, as well as goblet cell hyperplasia, in polyp tissues and normal controls. As shown in Fig. 1, the mean number of IL-17A+ cells per HPF was 6.7[2.9, 11.8] in polyp tissues and 1.6[0.8, 2.4] in normal controls; the mean staining score of MUC5AC was 2.2[1.7, 3.0] in polyp tissues and 0.6[0.4, 1.1] in normal controls. Both IL-17A and MUC5AC immunostaining were significantly increased in polyp tissues compared with the normal controls (p<0.05). Accordingly, we observed more PAS+ epithelial cells in polyp tissues, indicating an enhanced goblet cell hyperplasia. The PAS staining index in polyp tissues was 1.9[1.3, 2.2] and was significantly different than in normal controls with a staining index of 0.7[0.4, 1.2] (p<0.05). By setting the median of IL-17A+ cells in polyp tissues as the cutoff value (6.7/HPFs), we subdivided them into two subgroups: IL-17Ahigh (n = 12) and IL-17low (n = 13). Consequently, the MUC5AC staining score and PAS staining index were significantly higher in IL-17Ahigh subgroup than those in IL-17low subgroup (p<0.05). These findings suggested that IL-17A might contribute to MUC5AC expression and goblet cell hyperplasia in polyp tissues.


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)

PAS staining and immunostaining of IL-17A and MUC5AC in polyp tissues and normal controls.(A) Representative results of PAS staining and IHC staining of MUC5AC and IL-17A in polyp tissues and normal controls are shown (magnification, 200×). (B) The mean number of IL-17+ cells in polyp tissues and normal controls. (C) The PAS staining index in polyp tissues and normal controls. (D) The MUC5AC staining score in polyp tissues and normal controls. (E) The association between IL-17A and the PAS staining index in polyp tissues. (F) The association between IL-17A and MUC5AC staining scores in polyp tissues. 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-g001: PAS staining and immunostaining of IL-17A and MUC5AC in polyp tissues and normal controls.(A) Representative results of PAS staining and IHC staining of MUC5AC and IL-17A in polyp tissues and normal controls are shown (magnification, 200×). (B) The mean number of IL-17+ cells in polyp tissues and normal controls. (C) The PAS staining index in polyp tissues and normal controls. (D) The MUC5AC staining score in polyp tissues and normal controls. (E) The association between IL-17A and the PAS staining index in polyp tissues. (F) The association between IL-17A and MUC5AC staining scores in polyp tissues. Data are expressed as the medians (IQRs).
Mentions: Because IL-17A has been proposed to be significantly upregulated in nasal polyps, we firstly examined the expression of IL-17A and MUC5AC, as well as goblet cell hyperplasia, in polyp tissues and normal controls. As shown in Fig. 1, the mean number of IL-17A+ cells per HPF was 6.7[2.9, 11.8] in polyp tissues and 1.6[0.8, 2.4] in normal controls; the mean staining score of MUC5AC was 2.2[1.7, 3.0] in polyp tissues and 0.6[0.4, 1.1] in normal controls. Both IL-17A and MUC5AC immunostaining were significantly increased in polyp tissues compared with the normal controls (p<0.05). Accordingly, we observed more PAS+ epithelial cells in polyp tissues, indicating an enhanced goblet cell hyperplasia. The PAS staining index in polyp tissues was 1.9[1.3, 2.2] and was significantly different than in normal controls with a staining index of 0.7[0.4, 1.2] (p<0.05). By setting the median of IL-17A+ cells in polyp tissues as the cutoff value (6.7/HPFs), we subdivided them into two subgroups: IL-17Ahigh (n = 12) and IL-17low (n = 13). Consequently, the MUC5AC staining score and PAS staining index were significantly higher in IL-17Ahigh subgroup than those in IL-17low subgroup (p<0.05). These findings suggested that IL-17A might contribute to MUC5AC expression and goblet cell hyperplasia in polyp tissues.

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