Transcriptomics

Dataset Information

7

Transcription profiling by array of human peripheral blood mononuclear cells from volunteers exposed to diesel exhaust inhalation


ABSTRACT: Background: Diesel exhaust (DE) is the primary source of urban fine particulate matter, which has been associated with cardiovascular disease in epidemiological studies. These effects may be related to oxidative stress and systemic inflammation with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. Objectives: We conducted an exploratory study using microarray techniques to analyze whether global gene expression in peripheral blood mononuclear cells (PBMCs) can inform on potential mechanisms of effect of DE inhalation. Methods: In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in two-hour sessions. We isolated RNA (Trizol/Qiagen method) form PBMCs before, and two times after each exposure. RNA samples were arrayed using the Affymetrix® platform (GeneChip® Human Genome U133 Plus 2.0 Array). Results: Microarray analyses were conducted on five subjects with available RNA sample form exposures to FA and to the highest DE inhalation (200 µg/m³ of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets with significant evidence for differential expression (more than 1.5-fold up or down regulated with p < 0.05) were identified. These include genes involved in inflammatory response (e.g., IL8RA, TNFAIP6, FOS), oxidative stress (e.g., HMOX1, BAX, PRDX1,), and in biochemical pathways like mitogen-activated protein kinases (MAPK) and tight junction pathways. Conclusions: These data suggest that DE may exert time-dependent changes in gene expression in PBMCs in healthy individuals. Genes that may be affected by DE inhalation are involved in inflammatory and oxidative stress processes. Experiment Overall Design: We conducted a crossover, double-blind experiment, randomized to order of DE and filtered-air (FA) exposure with each participant exposed on four different days to each of four conditions: FA and DE calibrated to 50µg/m3 (DE50), 100µg/m3 (DE100), and 200µg/m3 (DE200) of fine particulate matter (PM2.5- particles with aerodynamic diameter 2.5µm or less). Exposure sessions were conducted at least 2 weeks apart.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: Richard Beyer  

PROVIDER: E-GEOD-7462 | ArrayExpress | 2008-06-15

SECONDARY ACCESSION(S): GSE7462PRJNA100207

REPOSITORIES: GEO, ArrayExpress

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Publications

Diesel exhaust inhalation and assessment of peripheral blood mononuclear cell gene transcription effects: an exploratory study of healthy human volunteers.

Peretz Alon A   Peck Erin C EC   Bammler Theo K TK   Beyer Richard P RP   Sullivan Jeffrey H JH   Trenga Carol A CA   Srinouanprachnah Sengkeo S   Farin Federico M FM   Kaufman Joel D JD  

Inhalation toxicology 20071101 14


Ambient fine particulate matter has been associated with cardiovascular and other diseases in epidemiological studies, and diesel exhaust (DE) is a major source of urban fine particulate matter. Air pollution's cardiovascular effects have been attributed to oxidative stress and systemic inflammation, with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. We conducted a pilot study using microarray techniqu  ...[more]

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