Mechanisms of glucocorticoid receptor signaling during inflammation.
Glucocorticoids are among the most widely prescribed anti-inflammatory drugs. They act by binding to the glucocorticoid receptor (GR) that, upon activation, translocates to the nucleus and either stimulates or inhibits gene expression. GR inhibition of many proinflammatory response genes occurs through induction of the synthesis of anti-inflammatory proteins as well as through repression of proinflammatory transcription factors, such as nuclear factor-kappaB (NF-kappaB) or activator protein-1 (AP-1). In this review, we discuss the molecular mechanisms underlying GR inhibition of inflammatory responses, with an emphasis on repression of NF-kappaB and AP-1 and their respective signaling pathways.
Smoak
Kathleen A
KA
Department of Health and Human Services, Laboratory of Signal Transduction, National Institute of Environmental Health Services, National Institutes of Health, Building 101, Research Triangle Park, NC 27709, USA.
Cidlowski
John A
JA
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D005938:Glucocorticoids; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1