Diesel exhaust particles modulate vascular endothelial cell permeability: implication of ZO-1 expression.
Exposure to air pollutants increases the incidence of cardiovascular disease. Recent toxicity studies revealed that ultra-fine particles (UFP, d(p)<100-200 nm), the major portion of particulate matter (PM) by numbers in the atmosphere, induced atherosclerosis. In this study, we posited that variations in chemical composition in diesel exhausted particles (DEP) regulated endothelial cell permeability to a different extent. Human aortic endothelial cells (HAEC) were exposed to well-characterized DEP (d(p)<100 nm) emitted from a diesel engine in either idling mode (DEP1) or in urban dynamometer driving schedule (UDDS) (DEP2). Horse Radish Peroxidase-Streptavidin activity assay showed that DEP2 increased endothelial permeability to a greater extent than DEP1 (control=0.077+/-0.005, DEP1=0.175+/-0.003, DEP2=0.265+/-0.006, n=3, p<0.01). DEP2 also down-regulated tight junction protein, Zonular Occludin-1 (ZO-1), to a greater extent compared to DEP1. LDH and caspase-3 activities revealed that DEP-mediated increase in permeability was not due to direct cytotoxicity, and DEP-mediated ZO-1 down-regulation was not due to a decrease in ZO-1 mRNA. Hence, our findings suggest that DEP1 vs. DEP2 differentially influenced the extent of endothelial permeability at the post-translational level. This increase in endothelium permeability is implicated in inflammatory cell transmigration into subendothelial layers with relevance to the initiation of atherosclerosis.
Li
Rongsong
R
Department of Biomedical Engineering, Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Ning
Zhi
Z
Cui
Jeffrey
J
Yu
Fei
F
Sioutas
Constantinos
C
Hsiai
Tzung
T
D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D052638:Particulate Matter / Q000633:toxicity*; D010539:Permeability; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D052638:Particulate Matter; D010750:Phosphoproteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; D001335:Vehicle Emissions; D062826:Zonula Occludens-1 Protein