Rui Wu1, Xuanchen Liu2, Jianyong Yin1, Huijuan Wu3, Xiulei Cai4, Niansong Wang5, Youcun Qian6, Feng Wang7. 1. Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. 2. Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Jiangsu University Affiliated Shanghai Eighth People's Hospital, Shanghai 200233, China. 3. Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 4. College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China. 5. Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: wangniansong2008@163.com. 6. Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China. 7. Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Jiangsu University Affiliated Shanghai Eighth People's Hospital, Shanghai 200233, China. Electronic address: zyzwq1030@163.com.
Abstract
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.
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.
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