Inhibition of Macrophage Migration Inhibitory Factor (MIF) tautomerase activity suppresses Microglia-mediated inflmmatory responses.

Inhibition of Macrophage Migration Inhibitory Factor (MIF) tautomerase activity suppresses Microglia-mediated inflmmatory responses.

Clin Exp Pharmacol Physiol. 2016 Aug 20;

Authors: Zhang Y, Gu R, Jia J, Hou T, Zheng L, Zhen X

Abstract
Macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, is a key regulator in both innate and acquired immunity system. 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 have identified that 3-[(biphenyl-4-ylcarbonyl)carbamothioyl]amino benzoic acid (Z-590) exhibited a potent inhibitory activity against MIF. In this study, we investigated the effect of Z-590 on lipopolysaccharide (LPS)-activated microglial cell activation. Our results demonstrated Z-590 significantly decreased the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, interleukin (IL)-1β, cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS) as well as reactive oxygen species (ROS) involved in inhibiting MAKPs signaling 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 indicated that MIF inhibitor Z-590 elicits a potent inhibitor for microglia-mediated neuroinflammation. This article is protected by copyright. All rights reserved.

PMID: 27543936 [PubMed - as supplied by publisher]

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