Health & Environmental Research Online (HERO)


Print Feedback Export to File
2614284 
Journal Article 
Abstract 
Induction of phase I xenobiotic metabolism and pro-inflammatory gene expression in vascular endothelial cell by concentrated ambient particulate matter 
Aung, HH; Lame, MW; He, G; Denison, MS; Wilson, DW; Rutledge, JC 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A6784 
English 
WOS:000208771005403 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Epidemiologic studies associate exposure to ambient Particulate Matter (APM) with an increase in pulmonary and cardiovascular morbidity and mortality. The mechanism(s) by which APM precipitates vascular injury is unclear. APM is composed of salts, crustal elements, trace metals, and organic and inorganic carbon that includes polycyclic aromatic hydrocarbons (PAH) derived from combustion and atmospheric chemistry. We hypothesize that PM interacts with the pulmonary microvasculature to elicit characteristic patterns of gene responses that include up-regulation of endothelial cell pro-inflammatory reactions. To characterize endothelial gene responses, human pulmonary microvascular endothelial cells (HMVEC) were exposed to either flame generated carbon particles rich in PAH (Soot) or fine and ultrafine APM collected during summer and winter in a rural and urban setting in California’s San Joaquin Valley. RNA isolated from HPMVEC exposed for 3 hr to 10 ug/ml APM or Soot was analyzed using quantitative real-time RT-PCR. Expression of genes associated with xenobiotic metabolism, transcription factors, cytokines, and leukocyte adhesion were determined. APM exposure resulted in up-regulation of cytochrome P450 1A1 (CYP1A1), aldehyde dehydrogenase, prostaglandin-endoperoxide synthase 2, TCDD-inducible poly (ADP-ribose) polymerase (TIPARP), activating transcription factor 3, Chemokine (C-C motif) ligand 2 (CCL2), interleukin 6 (IL-6), intercellular adhesion molecule 1 (ICAM-1) and E-selectin. Treatment of with Soot induced strong expression of PAH response genes, CYP1A1 and TIPARP. Relative to synthetic Soot, APM had an equivalent PAH (CYP 1A1, TIPARP) but greater inflammatory (CCL2, IL-6, ICAM-1 and E-Selectin) gene expression. APM collected in summer had a more marked inflammatory gene response than winter while CYP 1A1 expression was greater in winter source APM from both sites. We also compared PM sources with a luciferase based Aryl hydrocarbon response (AhR)-transcription assay in a hepatocyte cell line. Both Soot and APM stimulated AhR driven luciferase expression with the response to Soot approximating that of the TCDD positive control. APM stimulus of the AhR response in HPMVC was confirmed by immunofluorescent detection of AhR nuclear translocation 1 hr after APM treatment. Our findings demonstrate that AhR mediated transcription of CYP 1A1 is a characteristic signature of HPMVC response to both synthetic and ambient particulates. Our results suggest pulmonary microvascular inflammatory responses are separately mediated by components of APM that are season specific. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010