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

被引：15

作者：

Lo, Chun-Yu ^{[1
,2
]}

Wang, Chun-Hua ^{[1
,2
]}

Wang, Chih-Wei ^{[3
]}

Chen, Chih-Jung ^{[4
,5
]}

Huang, Hung-Yu ^{[1
,2
]}

Chung, Fu-Tsai ^{[1
,2
,6
]}

Huang, Yu-Chen ^{[1
,2
]}

Lin, Chang-Wei ^{[1
,2
]}

Lee, Chung-Shu ^{[1
,2
,6
]}

Lin, Chun-Yu ^{[1
,2
]}

Lin, Chiung-Hung ^{[1
,2
]}

Chang, Po-Jui ^{[1
,2
]}

Lin, Ting-Yu ^{[1
,2
]}

Heh, Chih-Chen ^{[1
]}

He, Jung-Ru ^{[1
]}

Chung, Kian Fan ^{[7
,8
]}

机构：

[1] Chang Gung Mem Hosp, Dept Thorac Med, Taipei, Taiwan

[2] Chang Gung Univ, Coll Med, Taoyuan, Taiwan

[3] Chang Gung Mem Hosp, Dept Pathol, Taipei, Taiwan

[4] Taichung Vet Gen Hosp, Dept Pathol & Lab Med, Taichung, Taiwan

[5] Chung Shan Med Univ, Sch Med, Taichung, Taiwan

[6] Chang Gung Med Fdn, New Taipei Municipal TuCheng Hosp, New Taipei City, Taiwan

[7] Imperial Coll London, Natl Heart & Lung Inst, Airway Dis Sect, London, England

[8] Royal Brompton Hosp, Biomed Res Unit, London, England

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

关键词：

interleukin-17; idiopathic pulmonary fibrosis; sarcoidosis; cryptogenic organizing pneumonia (COP); corticosteroid insensitivity; glucocorticoid receptor-beta; STEROID RESISTANCE; PULMONARY-FIBROSIS; UP-REGULATION; IL-17; INFLAMMATION; CYTOKINES; MECHANISMS; INDUCTION; ISOFORM; ASTHMA;

D O I：

10.3389/fimmu.2022.905727

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-beta 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-beta and IL-17 expression and neutrophil infiltration. Radiographic progression after oral corticosteroid treatment was positively correlated with the expression in IL-17 and GR-beta/GR-alpha ratio in all patients (COP, sarcoidosis and IPF) and also within the IPF subgroup only. IL-17 expression level was positively associated with GR-beta and GR-beta/GR-alpha ratio. In MRC5 cells, exogenous IL-17 increased the production of collagen I and up-regulated GR-beta 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-beta/GR-alpha ratio by IL-17 could be associated with the relative corticosteroid-insensitivity of IPF.

引用

页数：11

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