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- Title
Inhibition of macrophage migration inhibitory factor ( MIF) tautomerase activity suppresses microglia-mediated inflammatory responses.
- Authors
Zhang, Yu; Gu, Ruinan; Jia, Jia; Hou, Tingjun; Zheng, Long Tai; Zhen, Xuechu
- 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.
- Subjects
MACROPHAGE migration inhibitory factor; INFLAMMATION prevention; DOPACHROME tautomerase; MICROGLIA; TUMOR necrosis factors; NERVOUS system immunology; NITRIC-oxide synthases
- Publication
Clinical & Experimental Pharmacology & Physiology, 2016, Vol 43, Issue 11, p1134
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12647