title: Inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity suppresses microglia-mediated inflammatory responses.
abstract: Macrophage migration inhibitory factor (MIF), a pleiotropic pro-inflammatory cytokine, is a key regulator in both innate and acquired immunity systems. MIF has become a promising drug target for inflammatory diseases. Apart from its cytokine activities, MIF is known to act as a d-dopachrome tautomerase. Our previous work has identified that 3-[(biphenyl-4-ylcarbonyl)carbamothioyl]amino benzoic acid (Z-590) exhibited a potent inhibitory activity against MIF. In this study, we investigate the effect of Z-590 on lipopolysaccharide (LPS)-activated microglial cell activation. Our results demonstrate that Z-590 significantly decreases the production of nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS) as well as reactive oxygen species (ROS) involved in inhibiting MAKPs signalling pathway in LPS-stimulated microglia cells. Furthermore, Z-590 reduced cytotoxicity of activated microglia toward HT-22 hippocampal cells in a microglia-conditioned medium system. Taken together, these results indicate that MIF inhibitor Z-590 elicits a potent inhibitor for microglia-mediated neuroinflammation.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric Diseases and the Collaborative Innovation Centre for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.|Department of Pharmacy, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric Diseases and the Collaborative Innovation Centre for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Ruinan
authors.initials: R
authors.lastname: Gu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric Diseases and the Collaborative Innovation Centre for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Tingjun
authors.initials: T
authors.lastname: Hou
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric Diseases and the Collaborative Innovation Centre for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China. zhenglongtai@suda.edu.cn.
authors.forename: Long Tai
authors.initials: LT
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric Diseases and the Collaborative Innovation Centre for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China. zhenxuechu@suda.edu.cn.
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse
keywords: macrophage migration inhibitory factor; microglia; neuroinflammation tautomerase activity