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- Title
Increased Interleukin-17 and Glucocorticoid Receptor-b Expression in Interstitial Lung Diseases and Corticosteroid Insensitivity.
- Authors
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
- Abstract
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-b and responsiveness to corticosteroid treatment in interstitial lung diseases. Methods: Immunohistochemical (IHC) staining was performed on formalin-fixed paraffinembedded (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-a 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.
- Subjects
CRYPTOGENIC organizing pneumonia; INTERSTITIAL lung diseases; INTERLEUKIN-17; IDIOPATHIC pulmonary fibrosis; SARCOIDOSIS; PULMONARY fibrosis; GLUCOCORTICOIDS
- Publication
Frontiers in Immunology, 2022, Vol 13, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2022.905727