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

作者：Zhang, Zhiyu; Zhang, Rong; Li, Linlang; Zhu, Lijun; Gao, Shiyuan; Lu, Qiran; Gu, Yihui; Zhang, Yu; Yang, Huicui; Hou, Tingjun; Zhen, Xuechu; Zheng, Long Tai^*

来源：Immunopharmacology and Immunotoxicology, 2018, 40(2): 149-157.

DOI：10.1080/08923973.2018.1424896

• Macrophage migration inhibitory factor
• Z-590
• adjuvant-induced arthritis (AIA)
• macrophage
• inflammation

Background: 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. @@@ 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-alpha and IL-6 in LPS-activated RAW 264.7 macrophage cells and markedly inhibited LPS-induced expression of TNF-alpha, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Z-590 also significantly reduced paw edema, serum level of TNF-alpha, 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.

• 出版日期2018
• 单位苏州大学; 浙江大学; 湖北医药学院