title: Macrophage migration inhibitory factor activates cyclooxygenase 2-prostaglandin E2 in cultured spinal microglia.
abstract: In our previous study, peripheral inflammatory stimulation evoked production of macrophage migration inhibitory factor (MIF) in the spinal cord and found spinal microglia are the major source of MIF in this context. Given the contribution of the activated-microglia to the inflammatory neuropathy plus the role for upregulated COX 2 expression and PGE(2) production in the severity of clinical manifestations of these neuroinflammatory conditions, we herein tested the hypothesis that in vitro MIF stimulation to spinal microglia could result in an activation of COX 2-PGE(2) system by MIF-CD74 interaction. We found MIF played roles in evoking COX 2 mRNA and protein expression in a dose-dependent manner correspondingly in changes in PGE(2) level in the cultured rat microglia, but these changes could be inhibited by genetic deletion of CD74. Finally, MIF-induced COX 2-PGE(2) activation could be blocked by selective inhibitors of p44/p42 and p38 MAPKs. These data highlight MIF/CD74 interaction induces upregulation of COX 2 expression and PGE(2) secretion in primary rodent microglia, and further this effect is associated with downstream activation of p38 and p44/p42 signaling cascades, and favors the role of MIF as a novel pathway for microglia-associated neuroinflammation.
authors.affiliation: Department of Biochemistry and Bioinformatics, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, China.
authors.forename: FuZhou
authors.initials: F
authors.lastname: Wang
authors.forename: HaiBo
authors.initials: H
authors.lastname: Wu
authors.forename: ShiQin
authors.initials: S
authors.lastname: Xu
authors.forename: XiRong
authors.initials: X
authors.lastname: Guo
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: XiaoFeng
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism* / Q000502:physiology; D004789:Enzyme Activation / Q000235:genetics; D005911:Gliosis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism / Q000502:physiology; D019746:Intramolecular Oxidoreductases / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology*; D017628:Microglia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009187:Myelitis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; C045084:invariant chain; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat; D015232:Dinoprostone