ELSEVIER Life Sciences, Vol. 62, Nos. 17/l& pp. 1707-1710,1998 C0pyrisht 0 1998 JSkvier Science Inc. Printed in the USA. All rights merved 0024-32Osp3 s19.00 t .OO PII SOO24-3205(98)00132-S MOLECULAR BIOLOGY OF MICROGLIA CYTOKINE AND CHEMOKINE RECEPTORS AND MICROGLIAL ACTIVATION Olivia Spleiss, Kurt Appel, Hendrik W.G.M. Boddeke*, Mathias Berger and Peter J. Gebicke-Haerter Dept. of Psychiatry, University of Freiburg, Hauptstr. 5, D-79104 Freiburg i.Br., F.R.G., *Novartis Pharma, Preclinical Research, CH-4002 Basel, Switzerland Summary Activation of brain microglial cells can be subdivided into a number of stages. Early stages likely are proliferation and migration to sites of cell damage. These two stages have been studied exemplarily on the IL-3 receptor P-subunit and on the CC-chcrnokine receptor 5 using molecular biological methods. First, IL-3 receptor p-subunit cDNA has been cloned in full length from rat microglia. Since cultured microglia are already activated to some extent, mRNA of this subunit has been detected in the isolated cells, but was absent in normal rat brain. Lipopolysaccharide (LPS) increased this mRNA in the cultured cells and LPS injected into the circulation of rats induced the mRNA specifically in brain microglia as revealed by in situ hybridizations. Next, we obtained partial cDNAs of receptor-coupled protein tyrosine kinases JAK 1 and JAK 2. These mRNAs were present both in cultured microglia and in rat brain, but were not influenced by LPS. Finally, a full-length cDNA of the rat chemokine receptor 5 has been obtained by PCR methodology. Its mRNA was increased by adminstration of LPS both in cultured microglia and in vivo. It is expected, that further investigations on these receptors could help to develop improved strategies to combat chronic inflammatory events in the brain. Z&y Wo&: microglia cytokine, fever induction, MC40 stroke model, IL-3 receptor, chemolcme receptor 5, Janus kinases, mRNA expression in sharp contrast to other organs of the body, the central nervous system is characterized by a highly immnnosnppresive environment. Although we are far from understanding the molecular mechanisms underlying the weak immune responses in the brain, renewed interest in microglial research some lo-15 years ago has led to a variety of promising data. Many investigators have focused research on events involved in microglial activation (1). Address for Correspondence: Peter J. Gebicke-Haertcr, Dept. of Psychiatry, University of Frciburg, Hauptstr. 8, D-79104 Freiburg i.Br., FRG Tel.: +49(761)270-6835 ; Fax : +49(761)270-6619 ; e-mail : Petcr_Gebicke-Haerter@psyallg.ukl.uni-frciburg.de