Synthetic glucocorticoids (GCs) are potent anti-inflammatory drugs that are used to treat various inflammatory diseases, including asthma and rheumatoid arthritis. Prolonged medical use of GCs is however hindered by the adverse side effects that can lead to e.g. diabetes and osteoporosis. GCs function by activating a transcription factor, GC receptor, which induces and represses genes. Anti-inflammatory actions of GCs are result from repression of inflammatory genes, while the side effects arise from activation of metabolic genes. While the mechanisms of gene induction in GC signaling are relatively well characterized, those of gene repression are not. We analyze the mechanisms behind the anti-inflammatory GC signaling in macrophages using state-of-the-art mass spectrometry and genome-wide techniques. We believe, that thorough understanding of the mechanisms of GC-mediated transcription regulation provides translational opportunities for novel and safer GC treatments.

2020

2024