Increased Interleukin-17 and Glucocorticoid Receptor-β Expression in Interstitial Lung Diseases and Corticosteroid Insensitivity.

Autor:	Lo CY; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Wang CH; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Wang CW; Department of Pathology, Chang Gung Memorial Hospital, Taipei, Taiwan., Chen CJ; Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.; School of Medicine, Chung Shan Medical University, Taichung, Taiwan., Huang HY; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Chung FT; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan.; New Taipei Municipal TuCheng Hospital (Managed by Chang Gung Medical Foundation), New Taipei City, Taiwan., Huang YC; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Lin CW; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Lee CS; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan.; New Taipei Municipal TuCheng Hospital (Managed by Chang Gung Medical Foundation), New Taipei City, Taiwan., Lin CY; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Lin CH; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Chang PJ; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Lin TY; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Heh CC; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan., He JR; Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan., Chung KF; Airway Disease Section, National Heart and Lung Institute, Imperial College London and Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jul 05; Vol. 13, pp. 905727. Date of Electronic Publication: 2022 Jul 05 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.905727
Abstrakt:	Background: Treatment 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. Objective: To determine the associations among expression of IL-17, glucocorticoid receptor-β and responsiveness to corticosteroid treatment in interstitial lung diseases. Methods: Immunohistochemical (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. Results: Compared 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. Conclusion: Up-regulation of GR-β/GR-α ratio by IL-17 could be associated with the relative corticosteroid-insensitivity of IPF. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Lo, Wang, Wang, Chen, Huang, Chung, Huang, Lin, Lee, Lin, Lin, Chang, Lin, Heh, He and Chung.)
Databáze:	MEDLINE
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