title: EGCG Attenuates Uric Acid-Induced Inflammatory and Oxidative Stress Responses by Medicating the NOTCH Pathway.
abstract: BACKGROUND
  The aim of this study is to investigate whether (-)-epigallocatechin-3-gallate (EGCG) can prevent the UA-induced inflammatory effect of human umbilical vein endothelial cells (HUVEC) and the involved mechanisms in vitro.
  
  
  METHODS
  HUVEC were subjected to uric acid (UA) with or without EGCG treatment. RT-PCR and western blots were performed to determine the level of inflammation marker. The antioxidant activity was evaluated by measuring scavenged reactive oxygen species (ROS). Functional studies of the role of Notch-1 in HUVEC lines were performed using RNA interference analyses.
  
  
  RESULTS
  UA significantly increased the expressions of IL-6, ICAM-1, TNF-α, and MCP-1 and the production of ROS in HUVEC. Meanwhile, the expression of Notch-1 and its downstream effects significantly increased. Using siRNA, inhibition of Notch-1 signaling significantly impeded the expressions of inflammatory cytokines under UA treatment. Interestingly, EGCG suppressed the expressions of inflammatory cytokines and the generation of ROS. Western blot analysis of Notch-1 showed that EGCG significantly decreased the expressions of inflammatory cytokines through Notch-1 signaling pathways.
  
  
  CONCLUSIONS
  In summary, our findings indicated that Notch-1 plays an important role in the UA-induced inflammatory response, and the downregulation of Notch-1 by EGCG could be an effective approach to decrease inflammation and oxidative stress induced by UA.
authors.affiliation: Nutrition Department, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Nutrition Department, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Nutrition Department, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Nutrition Department, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zong
authors.affiliation: Nutrition Department, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Li
authors.affiliation: Nutrition Department, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014527:Uric Acid / Q000633:toxicity*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051880:Receptors, Notch; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D014527:Uric Acid; D002392:Catechin; C045651:epigallocatechin gallate