Glucocorticoids suppress macrophage migration inhibitory factor (MIF) expression in a cell-type-specific manner.
MIF is a potent proinflammatory cytokine involved in inflammatory arthritis. Glucocorticoids (GC) have been reported to induce secretion of MIF in rodent cells, and as MIF counteracts the anti-inflammatory effects of GC, this has implications for human inflammatory disease. Transient transfection studies showed that the MIF promoter was repressed by dexamethasone (Dex) (10 nM) in CEM C7A cells, with up to 50% suppression by 100 nM. However, there was no regulation of the promoter by GC in A549 cells. We also found that subnanomolar concentrations of Dex suppressed MIF secretion, measured by ELISA, by 80% in both human T lymphoblasts (CEM C7A) and human lung epithelial cells (A549). Endogenous MIF mRNA was also repressed by GC in CEM C7A cells, measured both by Northern blot and quantitative RT-PCR assays, but there was no such regulation in A549 cells. This suggests that GC affects translation rather than transcription of MIF in A549 cells. These results contradict earlier results with the rat cell line RAW 264.7. Therefore, we analysed MIF secretion from RAW 264.7 cells but found no GC effect on secretion. Understanding how GC regulates MIF in a cell-type-dependent manner may give insights into GC-refractory human inflammatory diseases.
Alourfi
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Z
ARC Epidemiology Unit, Endocrine Sciences Research Group, Centre for Molecular Medicine, Faculty of Medicine, University of Manchester, UK.
Donn
R P
RP
Stevens
A
A
Berry
A
A
McMaster
A
A
Ray
D W
DW
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate