title: Sesquiterpene lactones inhibit advanced oxidation protein product-induced MCP-1 expression in podocytes via an IKK/NF-κB-dependent mechanism.
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.
authors: 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.
authors: Yan
authors: Y
authors: Zhao
authors: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors: Si-jia
authors: SJ
authors: Chen
authors: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors: Jian-cheng
authors: JC
authors: Wang
authors: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors: Hong-xin
authors: HX
authors: Niu
authors: Department of Nephrology, Zhumadian Central Hospital, Zhumadian, Henan 463000, China.
authors: Qian-qian
authors: QQ
authors: Jia
authors: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors: Xiao-wen
authors: XW
authors: Chen
authors: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors: Xiao-yan
authors: XY
authors: Du
authors: Department of Traditional Chinese Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors: Lu
authors: L
authors: Lu
authors: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors: Bo
authors: B
authors: Huang
authors: College of Pharmacy, The State Key Laboratory of Elemento-Organic Chemistry, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors: Quan
authors: Q
authors: Zhang
authors: College of Pharmacy, The State Key Laboratory of Elemento-Organic Chemistry, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors: Yue
authors: Y
authors: Chen
authors: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors: Hai-bo
authors: HB
authors: Long
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050199:Podocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D062107:Advanced Oxidation Protein Products; D018932:Chemokine CCL2; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007783:Lactones; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D012717:Sesquiterpenes; D000072000:NF-KappaB Inhibitor alpha