Glucocorticoid modulation of human monocyte/macrophage function: control of TNF-alpha secretion.
Glucocorticoids suppress many functions in activated monocyte/macrophages, including the release of TNF-alpha. This is likely to contribute to the efficacy of glucocorticoids in some inflammatory diseases, such as rheumatoid arthritis, where TNF-alpha contributes to pathogenesis. Glucocorticoids suppress the activity of reporters which include TNF-alpha promoter regions and modify the activity of NF-kappa B family transcription factors in activated human monocytic cell lines, suggesting effects of glucocorticoids on TNF-alpha gene transcription. In addition, glucocorticoids have been reported to antagonise the enhanced translational efficiency of TNF-alpha mRNA which occurs at least after stimulation of murine monocytic cells. It is likely, therefore, that glucocorticoids act at several points in stimulated monocyte/ macrophages to reduce TNF-alpha secretion. Understanding glucocorticoid control of TNF-alpha secretion may explain some of the variability in response to GC in inflammatory diseases and may reveal means of inducing glucocorticoid-like anti-inflammatory effects in monocyte/macrophages without exposing other tissues to the adverse effects of glucocorticoids.
Joyce
D A
DA
Department of Pharmacology, University of Western Australia, Nedlands. djoyce@receptor.pharm.uwa.edu.au
Steer
J H
JH
Abraham
L J
LJ
D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D003907:Dexamethasone / Q000494:pharmacology; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone