EPA Science Inventory

Transcriptional Endothelial Biosensor Response to Diesel-Induced Plasma Compositional Changes

Citation:

Campe, M., M. Madden, J. Schisler, AND M. Willis. Transcriptional Endothelial Biosensor Response to Diesel-Induced Plasma Compositional Changes. Presented at American Thoracic Society (ATS) Meeting, San Diego, CA, May 16 - 21, 2014.

Description:

Air pollution, especially emissions derived from traffic sources, is associated with adverse cardiovascular outcomes. However, it remains unclear how inhaled factors drive an extrapulmonary pathology, as the lung is an effective barrier for solid particulates and many gases. Previously, using plasma from healthy human subjects exposed to diesel exhaust under controlled conditions, we found that canonical inflammatory response transcripts of interleukin-8 (IL-8), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were elevated in endothelial cells treated with plasma obtained after exposure compared with pre-exposure samples or filtered air (sham) exposures. While the findings confirmed the presence of bioactive factor(s) in the plasma after diesel inhalation, we wanted to better examine the complete genomic response to investigate 1) major responsive transcripts and 2) collected response pathways and ontogeny that may help to refine this method. Thus, we assayed previousy collected RNA with microarray chips, examining the responses of cultured endothelial cells to plasma obtained from 6 healthy human subjects exposed to 100 μg/m3 diesel exhaust or filtered air for 2 h on separate occasions. In addition to pre-exposure baseline samples, we investigated samples obtained immediately post and 24h post exposure. Primary human coronary artery endothelial cells were grown to confluence and treated with 10% plasma for 24 h, followed by isolation of RNA for microarrays. Microarray analysis of the coronary artery endothelial cells challenged with plasma identified 320 genes significantly altered when challenged with plasma from 1 and 24 hours post-diesel exhaust exposure, compared to baseline matched plasma. Transfac analysis of the differentially expressed genes identified 168 transcripts with E2F transcription factor promoter regions and 50 with NFκB transcription promoter regions (p values=0.0003 and 0.004, respectively). These outcomes are consistent with our recent findings that plasma contains bioactive and inflammatory factors following pollutant inhalation and provide a novel pathway to explain the well-reported extrapulmonary toxicity of ambient air pollutants. [This is an abstract of a proposed presentation and may not reflect official US EPA policy.]

Purpose/Objective:

To determine if diesel exhaust alone can prime extrapulmonary cells to alter their inflammatory status

URLs/Downloads:

CAMPEN ABSTRACT 2014 ATS.PDF   (PDF,NA pp, 352.975 KB,  about PDF)

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Completion Date: 05/20/2014
Record Last Revised: 05/20/2014
Record Created: 05/20/2014
Record Released: 05/20/2014
OMB Category: Other
Record ID: 276260

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

ENVIRONMENTAL PUBLIC HEALTH DIVISION

CLINICAL RESEARCH BRANCH