Glucocorticoid modulation of human monocyte/macrophage function: Control of TNF-alpha secretion

被引:95
作者
Joyce, DA
Steer, JH
Abraham, LJ
机构
[1] SIR CHARLES GAIRDNER HOSP,DEPT CLIN PHARMACOL & TOXICOL,NEDLANDS,WA 6009,AUSTRALIA
[2] UNIV WESTERN AUSTRALIA,DEPT BIOCHEM,NEDLANDS,WA 6907,AUSTRALIA
关键词
glucocorticoids; TNF-alpha; macrophage; transcription factors; promoter;
D O I
10.1007/s000110050222
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:447 / 451
页数:5
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