Glucocorticoids: new mechanisms and future agents.
Glucocorticoids are widely used to treat inflammatory and immune diseases. The most common use of glucocorticoids today is in the treatment of asthma. Inhaled glucocorticoids are first-line treatment in adults and children with persistent asthma, the most common chronic airway inflammatory disease. Our knowledge of how glucocorticoids suppress inflammation is based on recent developments in understanding the fundamental mechanisms of gene transcription, namely recruitment of histone-modifying co-factors. The determination of the crystal structure of the ligand-binding domain of the human glucocorticoid receptor (GR) has advanced our understanding of how ligands interact with GR and provide a glimpse of a future of rational drug design based on "space-filling" structures with dissociated properties. This might have important clinical implications, leading to a better understanding of the inflammatory mechanisms of many diseases and might signal the development of new anti-inflammatory treatments in the future.
Adcock
Ian M
IM
Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse St., London SW3 6LY, UK. ian.adcock@imperial.ac.uk
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000502:physiology; D003460:Crystallization; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006657:Histones / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D002843:Chromatin; D005938:Glucocorticoids; D006657:Histones; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D020928:Mitogen-Activated Protein Kinases