title: Effects of ambient air particles on the endothelin system in human pulmonary epithelial cells (A549).
abstract: Inhalation of urban particles results in higher circulating levels of the vasoconstrictor peptide endothelin-1 (ET-1), which may account for the adverse cardiovascular impacts associated with air pollution. The objective of this study was to examine the direct effects of urban particles on the production of ET-1 by human epithelial cells (A549). A549 cells were exposed to TiO(2), SiO(2), Ottawa urban particulate matter EHC-93, and fractions of the urban particles. The levels of ET-1, interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) in the culture medium were detected by ELISA. The mRNA levels of preproET-1, endothelin converting enzyme (ECE-1), ETa receptor and ETb receptor, matrix metalloproteinase (MMP-2), tissue inhibitor of MMP (TIMP-2), and heat shock protein (HSP-70) were determined by quantitative real-time RT-PCR. Cluster analysis of the variables identified similarities in the patterns of effects. Cluster I comprised variables that were primarily inhibited by particles: ET-1 and MMP-2 mRNAs, ET-1 and bigET-1 peptides, and cell viability. Clusters II and III comprised variables that were either inhibited or induced, depending on the test material: HSP-70, ETaR and ECE mRNAs, and IL-8 and VEGF proteins. Cluster IV comprised variables that were mainly induced by particle preparations: ETbR and TIMP-2 mRNAs. The decreased expression of preproET-1 in A549 cells suggests that epithelial cells may not be the source of higher pulmonary ET-1 spillover in the circulation measured in vivo in response to inhaled urban particles. However, higher ECE-1 in A549 cells after exposure to particles suggests an increased ability to process bigET-1 into the mature ET-1 peptide, while increased receptor expression implies higher responsiveness. The increased release of IL-8 and VEGF by epithelial cells in response to particles could possibly upregulate ET-1 production in the adjacent pulmonary capillary endothelial cells, with concomitant increased ET-1 spillover in the systemic circulation.
authors.affiliation: Safe Environments Programme, Health Canada, Ottawa, Ontario.
authors.forename: V
authors.initials: V
authors.lastname: Chauhan
authors.forename: D
authors.initials: D
authors.lastname: Breznan
authors.forename: E
authors.initials: E
authors.lastname: Thomson
authors.forename: S
authors.initials: S
authors.lastname: Karthikeyan
authors.forename: R
authors.initials: R
authors.lastname: Vincent
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004391:Dust; D019332:Endothelin-1 / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D015999:Multivariate Analysis; D011650:Pulmonary Alveoli; D017466:Receptors, Endothelin / Q000378:metabolism; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D004391:Dust; D019332:Endothelin-1; D016209:Interleukin-8; D017466:Receptors, Endothelin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes