Gene expression profile in circulating mononuclear cells after exposure to ultrafine carbon particles.
BACKGROUND
Exposure to particulate matter (PM) is associated with systemic health effects, but the cellular and molecular mechanisms are unclear.


OBJECTIVE
We hypothesized that, if circulating mononuclear cells play an important role in mediating systemic effects of PM, they would show gene expression changes following exposure.


METHODS
Peripheral blood samples were collected before (0 h) and at 24 h from healthy subjects exposed to filtered air (FA) and ultrafine carbon particles (UFPs, 50 microg/m(3)) for 2 h in a previous study (n = 3 each). RNA from mononuclear cell fraction (> 85% lymphocytes) was extracted, amplified and hybridized to Affymetrix HU133 plus 2 microarrays. Selected genes were confirmed in five additional subjects from the same study.


RESULTS
We identified 1713 genes (UFP 24 h vs. FA 0 and 24 h, P < 0.05, false discovery rate of 0.01). The top 10 upregulated genes (fold) were CDKN1C (1.86), ZNF12 (1.83), SRGAP2 (1.82), FYB (1.79), LSM14B (1.79), CD93 (1.76), NCSTN (1.70), DUSP6 (1.69), TACC1 (1.68), and H2AFY (1.68). Upregulation of CDKN1C and SRGAP2 was confirmed by real-time-PCR. We entered 1020 genes with a ratio >1.1 or <-1.1 into the Ingenuity Pathway Analysis and identified pathways related to inflammation, tissue growth and host defense against environmental insults, such as, insulin growth factor 1 signaling, insulin receptor signaling and NF-E2-related factor-2-mediated oxidative stress response pathway.


CONCLUSIONS
Two-hour exposures to UFP produced gene expression changes in circulating mononuclear cells. These gene changes provide biologically plausible links to PM-induced systemic health effects, especially those in the cardiovascular system and glucose metabolism.
Huang
Yuh-Chin T
YC
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. huang002@mc.duke.edu
Schmitt
Michael
M
Yang
Zhonghui
Z
Que
Loretta G
LG
Stewart
Judith C
JC
Frampton
Mark W
MW
Devlin
Robert B
RB
D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D002244:Carbon / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010316:Particle Size; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
D000393:Air Pollutants; D002244:Carbon