title: AOPPs induce MCP-1 expression by increasing ROS-mediated activation of the NF-κB pathway in rat mesangial cells: inhibition by sesquiterpene lactones.
abstract: BACKGROUND
  Monocyte chemoattractant protein-1 (MCP-1) plays an important role in extracellular matrix accumulation through macrophage recruitment and activation in the development and progression of diabetic nephropathy. Therefore, this study examined whether advanced oxidation protein products (AOPPs) are involved in nuclear factor-κB (NF-κB) activation and MCP-1 mRNA and protein expression in mesangial cells (MCs) and evaluated the effects of derivatives of sesquiterpene lactones (SLs) on AOPP-induced renal damage.
  
  
  METHODS
  MCP-1 mRNA and protein expression in MCs were determined by quantitative real-time PCR and ELISA, respectively. The level of intracellular reactive oxygen species (ROS) was determined by flow cytometry. The protein expression of tubulin, P47, NF-κB p65, phospho-NF-κB p65, IκB, phospho-IκB, IKKβ and phospho-IKKβ was evaluated by Western blot.
  
  
  RESULTS
  AOPPs caused oxidative stress in MCs and activated the NF-κB pathway by inducing IκBα phosphorylation and degradation. Inhibition of ROS by SOD (ROS inhibitor) blocked the AOPP-mediated NF-κB pathway. Moreover, the inhibition of AOPP-induced overproduction of MCP-1 mRNA and protein was associated with inhibition of IκBα degradation by SLs.
  
  
  CONCLUSIONS
  AOPPs induce MCP-1 expression by activating the ROS/NF-κB pathway and can be inhibited by SLs. These findings may provide a novel approach to treat inflammatory and immune renal diseases, including diabetic nephropathy.
authors.affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Si-Jia
authors.initials: SJ
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Long
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Jia
authors.forename: Jia-Dai
authors.initials: JD
authors.lastname: Zhai
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Long
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D062107:Advanced Oxidation Protein Products; D018932:Chemokine CCL2; D007783:Lactones; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D019255:NADPH Oxidases; D051550:I-kappa B Kinase