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

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
Předmět:
Zdroj: Frontiers in Immunology; 7/5/2022, Vol. 13, p1-11, 11p
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-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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index