Autor: |
Chun-Yu Lo, Chun-Hua Wang, Chih-Wei Wang, Chih-Jung Chen, Hung-Yu Huang, Fu-Tsai Chung, Yu-Chen Huang, Chang-Wei Lin, Chung-Shu Lee, Chun-Yu Lin, Chiung-Hung Lin, Po-Jui Chang, Ting-Yu Lin, Chih-Chen Heh, Jung-Ru He, Kian Fan Chung |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
Frontiers in Immunology, Vol 13 (2022) |
Druh dokumentu: |
article |
ISSN: |
1664-3224 |
DOI: |
10.3389/fimmu.2022.905727 |
Popis: |
BackgroundTreatment responsiveness to corticosteroids is excellent for cryptogenic organizing pneumonia (COP) and sarcoidosis, but suboptimal for idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). We hypothesise that the differential expression of IL-17 contributes to variable corticosteroid sensitivity in different interstitial lung diseases.ObjectiveTo determine the associations among expression of IL-17, glucocorticoid receptor-β and responsiveness to corticosteroid treatment in interstitial lung diseases.MethodsImmunohistochemical (IHC) staining was performed on formalin-fixed paraffin-embedded (FFPE) lung tissues obtained by bronchoscopic, CT-guided or surgical biopsies, and quantified by both cell counting (% positive cells) by individuals and by software IHC Profiler plugin of ImageJ (opacity density score). We studied the effect of IL-17 on corticosteroid sensitivity in human fibroblast MRC5 cell line.ResultsCompared with specimens from patients with COP (n =13) and sarcoidosis (n =13), those from IPF patients (n = 21) had greater GR-β and IL-17 expression and neutrophil infiltration. Radiographic progression after oral corticosteroid treatment was positively correlated with the expression in IL-17 and GR-β/GR-α ratio in all patients (COP, sarcoidosis and IPF) and also within the IPF subgroup only. IL-17 expression level was positively associated with GR-β and GR-β/GR-α ratio. In MRC5 cells, exogenous IL-17 increased the production of collagen I and up-regulated GR-β expression and dexamethasone’s suppressive effect on collagen I production was impaired by IL-17, and silencing IL-17 receptor A gene attenuated the effect of IL-17.ConclusionUp-regulation of GR-β/GR-α ratio by IL-17 could be associated with the relative corticosteroid-insensitivity of IPF. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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