H Wu, Y Li, X Li, W Huang, Z Huang, X Lai, J Ma, Y Jiang, Y Zhang, L Chang, G Zhang
{"title":"IL-17A 通过激活 ERK/STAT3 通路破坏慢性鼻炎患者的鼻粘膜上皮屏障。","authors":"H Wu, Y Li, X Li, W Huang, Z Huang, X Lai, J Ma, Y Jiang, Y Zhang, L Chang, G Zhang","doi":"10.4193/Rhin24.127","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The mucosal epithelial barrier, the first line of immune defense, is vulnerable to allergens, pathogens, and inflammatory cytokines, contributing to CRS development. Our previous studies found high interleukin-17A(IL-17A) expression correlated with CRS severity and low glucocorticoid efficacy. The role of IL-17A in disrupting the nasal mucosal epithelial barrier leading to CRS remains unclear. We aimed to investigate how IL-17A promoting epithelial barrier damage and identify new treatment targets for CRS.</p><p><strong>Methodology: </strong>Nasal tissue samples from 36 CRSwNP, 34 CRSsNP, and 39 controls were examined for the expression of IL-17A and tight junction (TJ) proteins using qRT-PCR, immunohistochemistry and immunofluorescence. The integrity of TJs and signaling pathways activation were observed using western blot, immunofluorescence, TEER and FITCâ€\"FD4, transmission electron microscopy before and after IL-17A stimulation in human primary nasal epithelial cells (hNECs). Concurrently, studies were also conducted in an CRS mouse model induced by anti-IL-17A neutralizing antibody administration.</p><p><strong>Results: </strong>TJs expression in the nasal mucosa of CRS patients was lower than in controls. IL-17A stimulation reduced TJs expression and TEER while increasing hNECs permeability. Inhibition of the (ERK/STAT3) pathway reversed the downregulation of TJs and the disruption of the epithelial barrier induced by IL-17A stimulation. In the CRS mouse model, anti-IL-17A antibody treatment rescued the nasal mucosal epithelial barrier.</p><p><strong>Conclusions: </strong>IL-17A disrupts the nasal mucosal epithelial barrier by activating the ERK/STAT3 pathway in patients with CRS.</p>","PeriodicalId":21361,"journal":{"name":"Rhinology","volume":" ","pages":"726-738"},"PeriodicalIF":4.8000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IL-17A disrupts the nasal mucosal epithelial barrier in patients with chronic rhinosinusitis by activating the ERK/STAT3 pathway.\",\"authors\":\"H Wu, Y Li, X Li, W Huang, Z Huang, X Lai, J Ma, Y Jiang, Y Zhang, L Chang, G Zhang\",\"doi\":\"10.4193/Rhin24.127\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The mucosal epithelial barrier, the first line of immune defense, is vulnerable to allergens, pathogens, and inflammatory cytokines, contributing to CRS development. Our previous studies found high interleukin-17A(IL-17A) expression correlated with CRS severity and low glucocorticoid efficacy. The role of IL-17A in disrupting the nasal mucosal epithelial barrier leading to CRS remains unclear. We aimed to investigate how IL-17A promoting epithelial barrier damage and identify new treatment targets for CRS.</p><p><strong>Methodology: </strong>Nasal tissue samples from 36 CRSwNP, 34 CRSsNP, and 39 controls were examined for the expression of IL-17A and tight junction (TJ) proteins using qRT-PCR, immunohistochemistry and immunofluorescence. The integrity of TJs and signaling pathways activation were observed using western blot, immunofluorescence, TEER and FITCâ€\\\"FD4, transmission electron microscopy before and after IL-17A stimulation in human primary nasal epithelial cells (hNECs). Concurrently, studies were also conducted in an CRS mouse model induced by anti-IL-17A neutralizing antibody administration.</p><p><strong>Results: </strong>TJs expression in the nasal mucosa of CRS patients was lower than in controls. IL-17A stimulation reduced TJs expression and TEER while increasing hNECs permeability. Inhibition of the (ERK/STAT3) pathway reversed the downregulation of TJs and the disruption of the epithelial barrier induced by IL-17A stimulation. In the CRS mouse model, anti-IL-17A antibody treatment rescued the nasal mucosal epithelial barrier.</p><p><strong>Conclusions: </strong>IL-17A disrupts the nasal mucosal epithelial barrier by activating the ERK/STAT3 pathway in patients with CRS.</p>\",\"PeriodicalId\":21361,\"journal\":{\"name\":\"Rhinology\",\"volume\":\" \",\"pages\":\"726-738\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Rhinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4193/Rhin24.127\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OTORHINOLARYNGOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Rhinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4193/Rhin24.127","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OTORHINOLARYNGOLOGY","Score":null,"Total":0}
IL-17A disrupts the nasal mucosal epithelial barrier in patients with chronic rhinosinusitis by activating the ERK/STAT3 pathway.
Background: The mucosal epithelial barrier, the first line of immune defense, is vulnerable to allergens, pathogens, and inflammatory cytokines, contributing to CRS development. Our previous studies found high interleukin-17A(IL-17A) expression correlated with CRS severity and low glucocorticoid efficacy. The role of IL-17A in disrupting the nasal mucosal epithelial barrier leading to CRS remains unclear. We aimed to investigate how IL-17A promoting epithelial barrier damage and identify new treatment targets for CRS.
Methodology: Nasal tissue samples from 36 CRSwNP, 34 CRSsNP, and 39 controls were examined for the expression of IL-17A and tight junction (TJ) proteins using qRT-PCR, immunohistochemistry and immunofluorescence. The integrity of TJs and signaling pathways activation were observed using western blot, immunofluorescence, TEER and FITCâ€"FD4, transmission electron microscopy before and after IL-17A stimulation in human primary nasal epithelial cells (hNECs). Concurrently, studies were also conducted in an CRS mouse model induced by anti-IL-17A neutralizing antibody administration.
Results: TJs expression in the nasal mucosa of CRS patients was lower than in controls. IL-17A stimulation reduced TJs expression and TEER while increasing hNECs permeability. Inhibition of the (ERK/STAT3) pathway reversed the downregulation of TJs and the disruption of the epithelial barrier induced by IL-17A stimulation. In the CRS mouse model, anti-IL-17A antibody treatment rescued the nasal mucosal epithelial barrier.
Conclusions: IL-17A disrupts the nasal mucosal epithelial barrier by activating the ERK/STAT3 pathway in patients with CRS.
期刊介绍：
Rhinology serves as the official Journal of the International Rhinologic Society and is recognized as one of the journals of the European Rhinologic Society. It offers a prominent platform for disseminating rhinologic research, reviews, position papers, task force reports, and guidelines to an international scientific audience. The journal also boasts the prestigious European Position Paper in Rhinosinusitis (EPOS), a highly influential publication first released in 2005 and subsequently updated in 2007, 2012, and most recently in 2020.
Employing a double-blind peer review system, Rhinology welcomes original articles, review articles, and letters to the editor.
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