TY - JOUR T1 - Glucocorticoids exacerbate TGFß1 mediated fibrotic signalling in lung fibroblasts by inhibition of metalloproteinase expression and activity JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.LSC-2021.33 VL - 7 IS - suppl 6 SP - 33 AU - M M Khan AU - J Zukowska-Kasprzyk AU - B Neumann AU - A Halavatyi AU - C Tischer AU - P Haberkant AU - F Stein AU - F Jung AU - J Landry AU - J Lewis AU - R Pepperkok Y1 - 2021/03/11 UR - http://openres.ersjournals.com/content/7/suppl_6/33.abstract N2 - Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of tissues causes fibrosis. This leads to local disruption of tissue architecture, with ultimate organ failure. To this end, we conducted a high-throughput microscopy-based screen of an FDA approved drug library in primary human lung fibroblasts, aiming at discovering novel regulators of fibrillar collagen deposition in ECM. Here, TGFß1 was used as a pro-ECM depostion stimulating agent. In total 760 drugs were screened. Interestingly, the data analysis shows that glucocorticoids, a widely used anti-inflammatory class of drugs, enhances depostion of Collagen 1 relative to fibroblasts treated with TGFß1 alone. Multiomic analysis (transcriptomics and proteomics) of fibroblasts treated with TGFß1 and Prednisolone (a routinely prescribed glucocorticoid) showed downregulation of metalloproteinase expression. Using MMP activity assay, we confirm that the observed downregulation in MMP expression leads to corresponding decrease in pan MMP activity. We hypothesise, this inhibition of metalloproteinase activity when coupled to TGFß1 stimulation, enhances the depostion of fibrillar collagen in ECM. Furthermore, the observed glucocorticoid mediated enhanced depostion of collagen 1 might exacerbate lung dysfunction, in particular, in patients with Interstitial lung disease and inherently higher TGFß1 activity.FootnotesCite this article as ERJ Open Research 2021; 7: Suppl. 6, 33.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -