Glucocorticoid transcriptome in macrophages upon activation [RNA-seq]

Glucocorticoids (GCs) are lifesaving medicines prescribed to treat inflammatory diseases. GCs act on numerous cell types and tissue of the body, however, one of the most important effects are their ability to suppress the immune system. Synthetic glucocorticoids, exemplified by dexamethasone (Dex) and prednisone, rank among the most widely prescribed anti-inflammatory and immunomodulatory drugs globally. The therapeutic efficacy of glucocorticoids extents across a broad spectrum of immune diseases, including conditions like acute and chronic inflammation. The action of the glucocorticoids in immune cells is mediated by the glucocorticoid receptor (here after GR; encoded by Nr3c1 gene) that is a member of the nuclear receptor superfamily of ligand dependent transcription factors. Macrophages emerge as central targets for the anti-inflammatory actions of glucocorticoids during periods of inflammation. Macrophages play a pivotal role during hyperinflammation and cytokine storm, two processes intricately linked to NLRP3 inflammasome activation in human diseases. Upon activation macrophages undergo a process of transcriptional reprogramming to resolve inflammation and restore homeostasis. To elucidate how glucocorticoids impact the transcriptome of macrophages upon activation, RNA-seq was performed on RNA isolated from macrophages unpolarized (M0) and polarized to M1 and M2 profile from WT and GRKO treated with vehicle and Dex. In addition, M0 and LPS M1-like macrophages were treated with vehicle and Dex and then analyzed by Cut&Tag.