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单核细胞趋化蛋白-1 的调节作用和重要性。

The regulation and importance of monocyte chemoattractant protein-1.

机构信息

Unit of Internal Medicine, Department of Medicine, University of Perugia, Hospital 'Santa Maria della Misericordia', Perugia, Italy.

Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Curr Opin Hematol. 2018 Jan;25(1):44-51. doi: 10.1097/MOH.0000000000000389.

Abstract

PURPOSE OF REVIEW

Monocyte chemoattractant protein (MCP)-1, a chemokine regulating monocyte chemotaxis and T-lymphocyte differentiation by binding to the CC chemokine receptor 2 (CCR2), plays a crucial role in the pathogenesis of inflammatory diseases, atherosclerosis and cancer. This review summarizes the current knowledge on the regulation and importance of the MCP-1/CCR2 axis, focusing on the therapeutic potential of its inhibition.

RECENT FINDINGS

Differential modulation of MCP-1 and CCR2 lead to downstream activation pathways, pathogenetic to differing disease conditions characterized by dysregulated monocyte/macrophage tissue recruitment. Pharmacological targeting of the MCP-1/CCR2 axis has led to selective MCP-1/CCR2 antagonists that have now entered phase I/II clinical trials for the treatment of inflammatory diseases, atherosclerosis and cancer. The pleiotropic nonselective MCP-1/CCR2 inhibition by current pharmacological agents is thought to contribute to their anti-inflammatory and antiatherosclerotic effects that is also seen for nutraceutical compounds such as curcumin.

SUMMARY

MCP-1 has a critical role in regulating chemotaxis both in health and disease, with increasing interest in its pharmacological inhibition. However, the therapeutic efficacy and safety of targeting the MCP-1/CCR2 axis is still in evolution.

摘要

目的综述

单核细胞趋化蛋白-1(MCP-1)是一种趋化因子,通过与 CC 趋化因子受体 2(CCR2)结合,调节单核细胞趋化和 T 淋巴细胞分化,在炎症性疾病、动脉粥样硬化和癌症的发病机制中发挥着关键作用。本综述总结了目前关于 MCP-1/CCR2 轴的调节和重要性的知识,重点介绍了其抑制作用的治疗潜力。

最新发现

MCP-1 和 CCR2 的差异化调节导致下游激活途径的不同,从而导致以失调的单核细胞/巨噬细胞组织募集为特征的不同疾病状态的发病机制。MCP-1/CCR2 轴的药理学靶向已导致选择性 MCP-1/CCR2 拮抗剂进入 I/II 期临床试验,用于治疗炎症性疾病、动脉粥样硬化和癌症。目前药理学药物对 MCP-1/CCR2 的多效性非选择性抑制被认为有助于其抗炎和抗动脉粥样硬化作用,这在姜黄素等营养化合物中也有体现。

总结

MCP-1 在健康和疾病中都对趋化作用起着关键作用,对其药理学抑制作用的兴趣日益增加。然而,靶向 MCP-1/CCR2 轴的治疗效果和安全性仍在不断发展。

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