Effects of glucocorticoids on apoptosis and clearance of apoptotic cells.
The glucocorticoid (GC) drugs are one of the most commonly prescribed and effective anti-inflammatory agents used for the treatment of many inflammatory disorders through their ability to attenuate phlogistic responses. The glucocorticoid receptor (GCR) primarily mediates GC actions via activation or repression of gene expression. GCs directly induce the expression of proteins displaying anti-inflammatory activities. However, the likely predominant effect of GCs is the repression of multiple inflammatory genes that invariably are overexpressed during nonresolving chronic inflammation. Although most GC actions are mediated through regulation of transcription, rapid nongenomic actions have also been reported. In addition, GCs modulate inflammatory cell survival, inducing apoptosis in immature thymocytes and eosinophils, while delaying constitutive neutrophil apoptosis. Importantly, GCs promote noninflammatory phagocytosis of apoptotic cell targets, a process important for the successful resolution of inflammation. Here, the effects and mechanisms of action of GC on inflammatory cell apoptosis and phagocytosis will be discussed.
McColl
Aisleen
A
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK.
Michlewska
Sylwia
S
Dransfield
Ian
I
Rossi
Adriano G
AG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D004351:Drug Resistance; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D009000:Monocytes / Q000166:cytology; D010587:Phagocytosis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000502:physiology; D015533:Transcriptional Activation
D005938:Glucocorticoids; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases