Dataset Information

Ultrafine particles from diesel vehicle emissions at different driving cycles induce differential vascular pro-inflammatory responses: implication of chemical components and NF-kappaB signaling.

ABSTRACT:

Background

Epidemiological evidence supports the association between exposure to ambient particulate matter (PM) and cardiovascular diseases. Chronic exposure to ultrafine particles (UFP; Dp <100 nm) is reported to promote atherosclerosis in ApoE knockout mice. Atherogenesis-prone factors induce endothelial dysfunction that contributes to the initiation and progression of atherosclerosis. We previously demonstrated that UFP induced oxidative stress via c-Jun N-terminal Kinases (JNK) activation in endothelial cells. In this study, we investigated pro-inflammatory responses of human aortic endothelial cells (HAEC) exposed to UFP emitted from a diesel truck under an idling mode (UFP1) and an urban dynamometer driving schedule (UFP2), respectively. We hypothesize that UFP1 and UFP2 with distinct chemical compositions induce differential pro-inflammatory responses in endothelial cells.

Results

UFP2 contained a higher level of redox active organic compounds and metals on a per PM mass basis than UFP1. While both UFP1 and UFP2 induced superoxide production and up-regulated stress response genes such as heme oxygenease-1 (HO-1), OKL38, and tissue factor (TF), only UFP2 induced the expression of pro-inflammatory genes such as IL-8 (2.8 +/- 0.3-fold), MCP-1 (3.9 +/- 0.4-fold), and VCAM (6.5 +/- 1.1-fold) (n = 3, P < 0.05). UFP2-exposed HAEC also bound to a higher number of monocytes than UFP1-exposed HAEC (Control = 70 +/- 7.5, UFP1 = 106.7 +/- 12.5, UFP2 = 137.0 +/- 8.0, n = 3, P < 0.05). Adenovirus NF-kappaB Luciferase reporter assays revealed that UFP2, but not UFP1, significantly induced NF-kappaB activities. NF-kappaB inhibitor, CAY10512, significantly abrogated UFP2-induced pro-inflammatory gene expression and monocyte binding.

Conclusion

While UFP1 induced higher level of oxidative stress and stress response gene expression, only UFP2, with higher levels of redox active organic compounds and metals, induced pro-inflammatory responses via NF-kappaB signaling. Thus, UFP with distinct chemical compositions caused differential response patterns in endothelial cells.

SUBMITTER: Li R

PROVIDER: S-EPMC2859401 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Publications

Ultrafine particles from diesel vehicle emissions at different driving cycles induce differential vascular pro-inflammatory responses: implication of chemical components and NF-kappaB signaling.

Li Rongsong R Ning Zhi Z Majumdar Rohit R Cui Jeffery J Takabe Wakako W Jen Nelson N Sioutas Constantinos C Hsiai Tzung T

Particle and fibre toxicology 20100322

<h4>Background</h4>Epidemiological evidence supports the association between exposure to ambient particulate matter (PM) and cardiovascular diseases. Chronic exposure to ultrafine particles (UFP; Dp <100 nm) is reported to promote atherosclerosis in ApoE knockout mice. Atherogenesis-prone factors induce endothelial dysfunction that contributes to the initiation and progression of atherosclerosis. We previously demonstrated that UFP induced oxidative stress via c-Jun N-terminal Kinases (JNK) acti ...[more]

PMID: 20307321

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Project description:BackgroundEmissions from diesel vehicles and biomass burning are the principal sources of primary ultrafine particles (UFP). The exposure to UFP has been associated to cardiovascular and pulmonary diseases, including lung cancer. Although many aspects of the toxicology of ambient particulate matter (PM) have been unraveled, the molecular mechanisms activated in human cells by the exposure to UFP are still poorly understood. Here, we present an RNA-seq time-course experiment (five time point after single dose exposure) used to investigate the differential and temporal changes induced in the gene expression of human bronchial epithelial cells (BEAS-2B) by the exposure to UFP generated from diesel and biomass combustion. A combination of different bioinformatics tools (EdgeR, next-maSigPro and reactome FI app-Cytoscape and prioritization strategies) facilitated the analyses the temporal transcriptional pattern, functional gene set enrichment and gene networks related to cellular response to UFP particles.ResultsThe bioinformatics analysis of transcriptional data reveals that the two different UFP induce, since the earliest time points, different transcriptional dynamics resulting in the activation of specific genes. The functional enrichment of differentially expressed genes indicates that the exposure to diesel UFP induces the activation of genes involved in TNFα signaling via NF-kB and inflammatory response, and hypoxia. Conversely, the exposure to ultrafine particles from biomass determines less distinct modifications of the gene expression profiles. Diesel UFP exposure induces the secretion of biomarkers associated to inflammation (CCXL2, EPGN, GREM1, IL1A, IL1B, IL6, IL24, EREG, VEGF) and transcription factors (as NFE2L2, MAFF, HES1, FOSL1, TGIF1) relevant for cardiovascular and lung disease. By means of network reconstruction, four genes (STAT3, HIF1a, NFKB1, KRAS) have emerged as major regulators of transcriptional response of bronchial epithelial cells exposed to diesel exhaust.ConclusionsOverall, this work highlights modifications of the transcriptional landscape in human bronchial cells exposed to UFP and sheds new lights on possible mechanisms by means of which UFP acts as a carcinogen and harmful factor for human health.

Project description:The present study examines the effects of fuel [an ultralow sulfur diesel (ULSD) versus a 20% v/v soy-based biodiesel-80% v/v petroleum blend (B20)], temperature, load, vehicle, driving cycle, and active regeneration technology on gas- and particle-phase carbon emissions from light and medium heavy-duty diesel vehicles (L/MHDDV). The study is performed using chassis dynamometer facilities that support low-temperature operation (-6.7 °C versus 21.7 °C) and heavy loads up to 12 000 kg. Organic and elemental carbon (OC-EC) composition of aerosol particles is determined using a thermal-optical technique. Gas- and particle-phase semivolatile organic compound (SVOC) emissions collected using traditional filter and polyurethane foam sampling media are analyzed using advanced gas chromatograpy/mass spectrometry methods. Study-wide OC and EC emissions are 0.735 and 0.733 mg/km, on average. The emissions factors for diesel vehicles vary widely, and use of a catalyzed diesel particle filter (CDPF) device generally mutes the carbon particle emissions in the exhaust, which contains ~90% w/w gas-phase matter. Interestingly, replacing ULSD with B20 did not significantly influence SVOC emissions, for which sums range from 0.030 to 9.4 mg/km for the L/MHDDVs. However, both low temperature and vehicle cold-starts significantly increase SVOCs in the exhaust. Real-time particle measurements indicate vehicle regeneration technology did influence emissions, although regeneration effects went unresolved using bulk chemistry techniques. A multistudy comparison of the toxic particle-phase polycyclic aromatic hydrocarbons (PAHs; molecular weight (MW) ≥ 252 amu) in diesel exhaust indicates emission factors that span up to 8 orders of magnitude over the past several decades. This study observes conditions under which PAH compounds with MW ≥ 252 amu appear in diesel particles downstream of the CDPF and can even reach low-end concentrations reported earlier for much larger HDDVs with poorly controlled exhaust streams. This rare observation suggests that analysis of PAHs in particles emitted from modern L/MHDDVs may be more complex than recognized previously.

Dataset Information

Ultrafine particles from diesel vehicle emissions at different driving cycles induce differential vascular pro-inflammatory responses: implication of chemical components and NF-kappaB signaling.

Background

Results

Conclusion

Publications

Ultrafine particles from diesel vehicle emissions at different driving cycles induce differential vascular pro-inflammatory responses: implication of chemical components and NF-kappaB signaling.

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