Endocrine Abstracts

Aim: To investigate glucocorticoid (Gc) regulation of MIF

Background: MIF is a potent proinflammatory cytokine involved in inflammatory arthritis. Previous work suggested that MIF was induced by low concentrations of Gc, and may counteract their anti-inflammatory effect. The relationship between MIF and Gc has not been investigated in human cells.

Methods: The human cell lines CEMC7A (T-lymphoblast) and A549 (lung epithelial) were used. MIF-luc (-779/+84) reporter gene was transiently transfected into cells, which were then incubated with dexamethasone. In addition endogenous MIF mRNA was measured using northern and RT-PCR approaches, and MIF secretion by ELISA.

Results: The MIF promoter was surprisingly repressed by dexamethasone (10nM) in CEM C7A cells, with up to 50% suppression by 100nM. There was no regulation of the promoter by Gc in A549 cells, despite the cells expressing the GR, and regulating other Gc reporter genes. Analysis of endogenous MIF mRNA also showed suppression in CEM C7A cells, but no regulation in A549 cells.

In contrast subnanomolar concentrations of dexamethasone suppressed MIF secretion by 80% in both CEM C7A and A549 cells. This result contradicts earlier work using the rat cell line, RAW 264.7. Therefore we analysed MIF expression in RAW 264.7 cells, and found no regulation of either MIF transcription, or secretion by dexamethasone.

Conclusions: We found no evidence for Gc induction of MIF expression in either human or rat cell lines. There was a clear, cell-type dependent difference in Gc regulation of MIF gene expression; the mechanism is now being sought. As MIF is expressed at sites of inflammation it is a potential target for the anti-inflammatory actions of Gc. Understanding how Gc regulation of MIF is cell-type dependent may give insights to refractory, human inflammatory diseases.