title: Protective Effects of N-Acetyl Cysteine against Diesel Exhaust Particles-Induced Intracellular ROS Generates Pro-Inflammatory Cytokines to Mediate the Vascular Permeability of Capillary-Like Endothelial Tubes.
abstract: Exposure to diesel exhaust particles (DEP) is associated with pulmonary and cardiovascular diseases. Previous studies using in vitro endothelial tubes as a simplified model of capillaries have found that DEP-induced ROS increase vascular permeability with rearrangement or internalization of adherens junctional VE-cadherin away from the plasma membrane. This allows DEPs to penetrate into the cell and capillary lumen. In addition, pro-inflammatory cytokines are up-regulated and mediate vascular permeability in response to DEP. However, the mechanisms through which these DEP-induced pro-inflammatory cytokines increase vascular permeability remain unknown. Hence, we examined the ability of DEP to induce permeability of human umbilical vein endothelial cell tube cells to investigate these mechanisms. Furthermore, supplementation with NAC reduces ROS production following exposure to DEP. HUVEC tube cells contributed to a pro-inflammatory response to DEP-induced intracellular ROS generation. Endothelial oxidative stress induced the release of TNF-α and IL-6 from tube cells, subsequently stimulating the secretion of VEGF-A independent of HO-1. Our data suggests that DEP-induced intracellular ROS and release of the pro-inflammatory cytokines TNF- α and IL-6, which would contribute to VEGF-A secretion and disrupt cell-cell borders and increase vasculature permeability. Addition of NAC suppresses DEP-induced ROS efficiently and reduces subsequent damages by increasing endogenous glutathione.
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Chung Yuan Christian University, Zhongli district, Taoyuan city, Taiwan; Center of Nanotechnology, Chung Yuan Christian University, Zhongli district, Taoyuan city, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Tseng
authors.affiliation: Department of Bioscience Technology, College of Science, Chung Yuan Christian University, Zhongli district, Taoyuan city, Taiwan.
authors.forename: Jing-Fen
authors.initials: JF
authors.lastname: Chang
authors.affiliation: Department of Bioscience Technology, College of Science, Chung Yuan Christian University, Zhongli district, Taoyuan city, Taiwan.
authors.forename: Jhih-Syuan
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Department of Bioscience Technology, College of Science, Chung Yuan Christian University, Zhongli district, Taoyuan city, Taiwan.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Joint program of Toxicology, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Marion K
authors.initials: MK
authors.lastname: Gordon
authors.affiliation: Center of Nanotechnology, Chung Yuan Christian University, Zhongli district, Taoyuan city, Taiwan; Department of Bioscience Technology, College of Science, Chung Yuan Christian University, Zhongli district, Taoyuan city, Taiwan.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chao
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000009:adverse effects; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D003545:Cysteine; D016207:Cytokines; D051547:Heme Oxygenase-1; D015850:Interleukin-6; D052638:Particulate Matter; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D001335:Vehicle Emissions; D000099152:Cadherin 5; C496541:HMOX1 protein, human