Sesquiterpene Lactones Inhibit Advanced Oxidation Protein Product-Induced MCP-1 Expression in Podocytes via an IKK-NF-κB-Dependent MechanismReportar como inadecuado




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Oxidative Medicine and Cellular Longevity - Volume 2015 2015, Article ID 934058, 13 pages -

Research Article

Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China

Department of Nephrology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, Hubei 441021, China

Department of Nephrology, Zhumadian Central Hospital, Zhumadian, Henan 463000, China

Department of Traditional Chinese Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China

College of Pharmacy, The State Key Laboratory of Elemento-Organic Chemistry, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China

Received 7 September 2014; Accepted 10 December 2014

Academic Editor: Vittorio Calabrese

Copyright © 2015 Yan Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy DN. Sesquiterpene lactones SLs, originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products AOPPs can induce the expression of chemokine monocyte chemoattractant protein- MCP- 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs parthenolide and its derivatives micheliolide, compound 1, and compound 2. MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKβ, phospho-IKKβ, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKβ and NF-κB p65, and promoted IκBα degradation. The IKK-NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases.





Autor: Yan Zhao, Si-jia Chen, Jian-cheng Wang, Hong-xin Niu, Qian-qian Jia, Xiao-wen Chen, Xiao-yan Du, Lu Lu, Bo Huang, Quan Zh

Fuente: https://www.hindawi.com/



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