Comparative gene responses to collected ambient particles in vitro: Endothelial responses

Hnin H. Aung, Michael W. Lame, Kishorchandra Gohil, Guochun He, Michael S. Denison, John C Rutledge, Dennis W Wilson

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Epidemiologic studies associate exposure to ambient particulate matter (APM) with increased cardiovascular mortality. Since both pulmonary inflammation and systemic circulation of ultrafine particles are hypothesized as initiating cardiovascular effects, we examined responses of potential target cells in vitro. Human aortic endothelial cells (HAEC) were exposed to 10 μg/ml fine and ultrafine APM collected in an urban setting in summer 2006 or winter 2007 in the San Joaquin Valley, California. RNA isolated after 3 h was analyzed with high-density oligonucleotide arrays. Summer APM treatment affected genes involved in xenobiotic and oxidoreductase activity, transcription factors, and inflammatory responses in HAEC, while winter APM had a robust xenobiotic but lesser inflammatory response. Real-time polymerase chain reaction analysis confirmed that particulate matter (PM)-treated HAEC increased mRNA levels of xenobiotic response enzymes CYP1A1, ALDH1A3, and TIPARP and cellular stress response transcription factor ATF3. Inflammatory response genes included E-selectin, PTGS2, CXCL-2 (MIP-2α), and CCL-2 (MCP-1). Multiplex protein assays showed secretion of IL-6 and MCP-1 by HAEC. Since induction of CYP1A1 is mediated through the ligand-activated aryl hydrocarbon receptor (AhR), we demonstrated APM induced AhR nuclear translocation by immunofluorescence and Western blotting and activation of the AhR response element using a luciferase reporter construct. Inhibitor studies suggest differential influences of polycyclic aromatic hydrocarbon signaling, ROS-mediated responses and endotoxin alter stress and proinflammatory endothelial cell responses. Our findings demonstrate gene responses correlated with current concepts that systemic inflammation drives cardiovascular effects of particulate air pollution. We also demonstrate a unique pattern of gene responses related to xenobiotic metabolism in PM-exposed HAEC.

Original languageEnglish (US)
Pages (from-to)917-929
Number of pages13
JournalPhysiological Genomics
Volume43
Issue number15
DOIs
StatePublished - Aug 2011

Keywords

  • Aryl hydrocarbon receptor
  • Cytochrome P450
  • Environmental particulate matter
  • Inflammation
  • Oligonucleotide arrays

ASJC Scopus subject areas

  • Physiology
  • Genetics

Fingerprint Dive into the research topics of 'Comparative gene responses to collected ambient particles in vitro: Endothelial responses'. Together they form a unique fingerprint.

  • Cite this