IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice
IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice
复制标题
IL-6 受体阻断通过抑制小鼠炎症小体改善糖尿病肾病
DOI：
10.1016/j.metabol.2018.01.002
复制
发表时间：
2018-06-01
影响因子：
9.8
通讯作者：
Wang, Feng
中科院分区：
文献类型：
--
作者：
Wu, Rui;Liu, Xuanchen;Wang, Feng
Background and Objective: Interleukin 6 (IL-6) has been identified as a key mediator in inflammation, immune responses and glucose metabolism. In this study, we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a mouse model of type 2 diabetes mellitus.Methods: Twelve week old male db/db mice were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and insulin resistance were assessed.Results: Db/db mice treated with Tocilizumab exhibited reduced proteinuria and glomerular mesangial matrix accumulation compared to db/db + IgG controls. Additionally, Tocilizumab suppressed inflammatory response, oxidative stress and the IL-6 signaling pathway in the diabetic kidneys. It is noteworthy that blockade of IL-6 receptor blunted the activation of NLRP3 inflammasome partly through inhibition of IL-17A. Furthermore, insulin resistance assessed by glucose tolerance test, was ameliorated by Tocilizumab treatment.Conclusions: The protective effects of an IL-6 receptor blockade against diabetic renal injury may be due to decreased insulin resistance and inhibition of the inflammasome. (C) 2018 Elsevier Inc. All rights reserved.
