Medical College of Korea University, Ansan Hospital, Division of Nephrology, Department of Internal Medicine, Ansan City, Korea.
Expert Opin Investig Drugs. 2011 Jun;20(6):745-56. doi: 10.1517/13543784.2011.575359. Epub 2011 Apr 6.
C-C chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1, and its receptor, C-C chemokine receptor 2 (CCR2), play important roles in various inflammatory diseases. Recently, it has been reported that the CCL2/CCR2 pathway also has an important role in the pathogenesis of metabolic syndrome through its association with obesity and related systemic complications.
This review focuses on the roles of CCR2 in the pathogenesis of adipose tissue inflammation and other organ damage associated with metabolic syndrome, which is still a matter of debate in many studies. It also covers the use of novel CCR2 antagonists as therapies in such conditions.
There is abundant experimental evidence that the CCL2/CCR2 pathway may be involved in chronic low-grade inflammation of adipose tissue in obesity and related metabolic diseases. Although animal models of diabetes and obesity, as well as human trials, have produced controversial results, there is continued interest in the roles of CCR2 inhibition in metabolic disease. Further identification of the mechanisms for recruitment and activation of phagocytes and determination of the roles of other chemokines are needed. Future study of these fundamental questions will provide a clearer understanding of adipose tissue biology and potential therapeutic targets for treatment of obesity-related metabolic disease, including diabetic nephropathy.
C-C 趋化因子配体 2(CCL2),也称为单核细胞趋化蛋白-1,及其受体 C-C 趋化因子受体 2(CCR2),在各种炎症性疾病中发挥重要作用。最近的研究表明,CCL2/CCR2 通路通过与肥胖和相关的全身性并发症相关联,在代谢综合征的发病机制中也具有重要作用。
本篇综述重点介绍了 CCR2 在代谢综合征相关脂肪组织炎症和其他器官损伤发病机制中的作用,这在许多研究中仍然存在争议。它还涵盖了新型 CCR2 拮抗剂在这些疾病中的治疗应用。
有大量的实验证据表明,CCL2/CCR2 通路可能参与肥胖和相关代谢疾病中脂肪组织的慢性低度炎症。尽管糖尿病和肥胖症的动物模型以及人体试验得出了相互矛盾的结果,但 CCR2 抑制在代谢疾病中的作用仍在持续受到关注。需要进一步确定招募和激活吞噬细胞的机制,并确定其他趋化因子的作用。对这些基本问题的进一步研究将提供对脂肪组织生物学和治疗肥胖相关代谢疾病(包括糖尿病肾病)的潜在治疗靶点的更清晰理解。