Expression and glucocorticoid regulation of macrophage migration inhibitory factor (MIF) in hippocampal and neocortical rat brain cells in culture

The biosynthesis of macrophage-migration inhibitory factor (MIF) and its re gulation by the glucocorticoid dexamethasone was examined in cultured hippo campal and neocortical embryonic rat cells. Using immunohistochemical metho ds, MIF was found to be localized in neuronal as well as in non-neuronal ce lls. During the whole 12 day culture period, levels of MIF transcripts were detectable in both hippocampal and neocortical cells with an apparent incr ease in extracellular MIF protein at the later time points examined. Treatm ent with even very low concentrations (10(-11) M) of dexamethasone did not alter MIF mRNA levels but resulted in a rapid release of intracellular MIF protein within 1 and 4 h and a subsequent replenishment after 24 h. These d ata suggest that glucocorticoids do not affect the transcriptional activity of the MIF gene but induce the secretion of the protein, which suggests a close functional relationship of both mediators in the CNS. (C) 2000 Elsevi er Science B.V. All rights reserved.