Brain Research 869 (2000) 25–30 www.elsevier.com / locate / bres Research report Expression and glucocorticoid regulation of macrophage migration inhibitory factor (MIF) in hippocampal and neocortical rat brain cells in culture a, a a b * ¨ Helmut Vedder , Jurgen-Christian Krieg , Birgit Gerlach , Diethard Gemsa , b Michael Bacher a Department of Psychiatry and Psychotherapy, Philipps-University, Rudolf-Bultmann-Str. 8, 35033 Marburg, Germany b Institute of Immunology, Philipps-University, Rudolf-Bultmann-Str. 8, 35033 Marburg, Germany Accepted 21 March 2000 Abstract The biosynthesis of macrophage-migration inhibitory factor (MIF) and its regulation by the glucocorticoid dexamethasone was examined in cultured hippocampal and neocortical embryonic rat cells. Using immunohistochemical methods, MIF was found to be localized in neuronal as well as in non-neuronal cells. During the whole 12 day culture period, levels of MIF transcripts were detectable in both hippocampal and neocortical cells with an apparent increase in extracellular MIF protein at the later time points examined. Treatment 211 with even very low concentrations (10 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 data 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.  2000 Elsevier Science B.V. All rights reserved. Theme: Endocrine and autonomic regulation Topic: Hypothalamic-pituitary-adrenal regulation Keywords: Macrophage migration inhibitory factor; Hippocampal cell; Neocortical cell; Neuron; Glucocorticoid 1. Introduction the lethality rate of rats after LPS injection and a concomi- tant treatment with MIF [4]. This increase was blocked by Macrophage migration inhibitory factor (MIF) was MIF antibodies [4], suggesting a specific role of MIF in the primarily characterized as a lymphokine produced by course of this type of host response. activated T-lymphocytes during delayed-type hyper- Other data extended the role of this cytokine and sensitivity reactions [5,9]. Recent studies have documented indicated an involvement in neuroendocrine–immunologi- a critical role for MIF in the course of immunological host cal interactions due to its localization in the pituitary and defence reactions since it is synthesized in activated T- its release from anterior pituitary cells after endotoxaemia cells [3] as well as in monocytes / macrophages after ([4], for review see: [6]). Thus, MIF may not only stimulation by a number of immunological compounds represent an important factor in the immune system, but such as mitogens, antigens, bacterial lipopolysaccharides, may also be expressed and become functional in the CNS. tumor necrosis factor-a and interferon-g [3,8]. Additional This assumption is also supported by studies indicating an studies even indicate a pivotal function in the regulation of involvement of MIF in neuroendocrine regulation and host defence mechanisms, as evidenced by an increase in neurological disease [1,21]. To gather more information, we here examined the cellular localization and regulation of MIF in cultured cells of the hippocampus and the *Corresponding author. Tel.: 149-6421-286-6429; fax: 149-6421-286- neocortex. Using established cell culture systems for these 8939. E-mail address: vedder@mailer.uni-marburg.de (H. Vedder) cells from the rat, we employed specific detection systems 0006-8993 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0006-8993(00)02336-2