Inhibition of macrophage migration inhibitory factor ( MIF ) tautomerase activity suppresses microglia‐mediated inflammatory responses

Summary 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 MAKP s 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.