Epigenomic effects of Glucocorticoids on Macrophages

Authors

• K Oh
• RA Gottschalk
• S Baek
• WS Lee
• GL Hager
• ID Fraser
• MH Sung

Abstract

It is well known that lipopolysaccharide (LPS) induces inflammatory signals while dexamethasone (Dex) induces anti-inflammatory signals through activation of glucocorticoid receptor (GR). Past studies have been centering on the antagonistic effects of LPS and Dex in inducing inflammatory versus anti-inflammatory responses (via NF-kappaB and GR). Previous data have shown that the treatment of Dex alone can introduce pronounced epigenomic effects on non-immune cell lines. However, it is unknown whether Dex may play a similar role in primary bone marrow derived macrophages (BMDMs) in presence of LPS treatment. The goal of the present work is to study whether Dex suppresses LPS-induced NF-kappaB response through epigenetic means, and possibly further understanding of possible synergy between Dex and LPS. Using a combination of chromatin accessibility, transcription factor binding and gene expression, and mathematical analysis and modeling, our analysis suggests different effects of Dex and LPS on chromatin state. Our study also provides insight on the effects of steroids in activated versus resting immune cells through epigenetic and transcriptional regulation.

Scientific Focus Area: Immunology

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