Macrophage migration inhibitory factor (MIF) inhibitor, Z-590 suppresses cartilage destruction in adjuvant-induced arthritis via inhibition of macrophage inflammatory activation.

Macrophage migration inhibitory factor (MIF) inhibitor, Z-590 suppresses cartilage destruction in adjuvant-induced arthritis via inhibition of macrophage inflammatory activation.

Immunopharmacol Immunotoxicol. 2018 Feb 15;:1-9

Authors: Zhang Z, Zhang R, Li L, Zhu L, Gao S, Lu Q, Gu Y, Zhang Y, Yang H, Hou T, Zhen X, Zheng LT

Abstract
INTRODUCTION: Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory mediator that is involved in the progression of rheumatoid arthritis (RA). Previously, we demonstrated a small molecule compound 3-[(biphenyl-4-ylcarbonyl) carbamothioyl] amino benzoic acid (Z-590) could inhibit MIF activity with docking-based virtual screening and experimental evaluation.
MATERIALS AND METHODS: The LPS activated RAW264.7 macrophage cells were used to determine the anti-inflammatory effects of Z-590 in vitro. A rat adjuvant-induced arthritis (AIA) model was used to determine the anti-arthritic effects of Z-590 in vivo.
RESULTS: MIF inhibitor Z-590 significantly inhibited the production of NO, TNF-α and IL-6 in LPS-activated RAW 264.7 macrophage cells and markedly inhibited LPS-induced expression of TNF-α, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Z-590 also significantly reduced paw edema, serum level of TNF-α, IL-6 and spleen index in the adjuvant-induced arthritis (AIA) rat model. Furthermore, Z-590 markedly ameliorated joint inflammation and articular cartilage damage in AIA rat model.
CONCLUSION: MIF inhibitor Z-590 possesses potent anti-arthritic activity through suppression of macrophage activation, and could be a potential therapeutic treatment for RA.

PMID: 29447014 [PubMed - as supplied by publisher]

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