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Understanding the health effects of isoprene-derived particulate matter enhanced by anthropogenic pollutants

Principal Investigator: 

University of North Carolina

This New Investigator Award study investigates the toxicity of fine particulate matter formed from the photochemical oxidation of isoprene, in indoor and outdoor smog-chamber facilities. Experiments will feature synthesized isoprene oxidation products, mixtures of isoprene, diesel PM and urban VOCs, and also urban (“high” NOx) and downwind-urban (“low” NOx) conditions with an acidic seed.

Funded under
In review

Abstract for the 2017 HEI Annual Conference

Assessing the Biological Effects of Isoprene-Derived Secondary Organic Aerosol (SOA) Enhanced by Anthropogenic Pollutants on Human Lung Cells 

Jason D. Surratt, Ying-Hsuan Lin, Maiko Arashiro, Amanda J. Kramer, Kenneth G. Sexton, Ilona Jaspers, Rebecca Fry, and Avram Gold

University of North Carolina–Chapel Hill, USA

Background SOA from the atmospheric oxidation of isoprene in the presence of acidic sulfate aerosol substantially contributes to fine particulate matter (PM2.5). Whether isoprene SOA contributes to the adverse health effects induced by exposure to PM2.5 reported in epidemiological studies is largely unknown. Isoprene-derived epoxides and hydroperoxides have been recently identified as key gaseous intermediates leading to SOA. We have evaluated the potential biological effects of the pure epoxides, hydroperoxides and selected SOA products as well as smog chamber-generated SOA constituents in an in vitro model of human airway epithelial cells (BEAS-2B) using both resuspension and direct deposition approaches.
Objectives The objective of this study was to evaluate the potential biological effects induced by exposure to isoprene-derived epoxides and hydroperoxides and their resultant SOA constituents based on the biological pathways hypothesized to link PM2.5 exposures to cardiopulmonary mortality, with a specific focus on oxidative stress and inflammation.
Methods Isoprene-derived epoxides, isoprene epoxydiols (IEPOX) and methacrylic acid epoxide (MAE), and hydroperoxides (ISOPOOH) were synthesized and directly injected into an indoor smog chamber facility that contained sulfate aerosol. Filter samples were collected and subsequently used for chemical characterization and resuspension. SOA was also generated in an outdoor smog chamber facility by naturally irradiating isoprene, NOx and acidified sulfate aerosol. Atmospherically relevant SOA compositions were generated from this mixture. SOA from both chambers was chemically characterized using gas chromatography and liquid chromatography interfaced to mass spectrometry. SOA constituents were extracted from filters and added directly to cell culture media for measures of cytotoxicity, oxidative stress and inflammation. Biological effects were also evaluated at the air-liquid interface using the UNC Electrostatic Aerosol Exposure System (EAVES). Cell viability and cytotoxicity were assessed using XTT and LDH assays. Transcriptional changes of inflammation-associated genes were assessed using quantitative real-time RT-PCR (qRT-PCR). Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) were selected as target genes for proinflammatory responses. In addition, the pathway-focused Human Oxidative Stress Plus RT² Profiler PCR Array with 84 oxidative stress-associated genes was performed. The dithiothreitol (DTT) assay was used to characterize the ROS generation potential of pure epoxides, hydroperoxides and SOA.
Results We show that isoprene-derived SOA constituents alter the expression of oxidative stress- and inflammation-associated genes in human lung cells under non-cytotoxic conditions. Isoprene-derived hydroperoxides induce stronger cytotoxic responses than epoxides and their respective hydrolysis products that yield SOA. We also found that isoprene SOA enriched the expression of nuclear factor erythroid 2-like 2 (NRF2)-mediated oxidative stress responses in human lung cells, with MAE- and ISOPOOH-derived SOA showing greater potency than IEPOX-derived SOA. Compared with diesel exhaust PM, isoprene-derived SOA had the same or higher ROS generation potential.
Conclusions Atmospherically-relevant compositions of isoprene-derived SOA alter the levels of oxidative stress-related gene expression within BEAS-2B cells. Our in vitro work reveals that there was an enrichment for altered expression of genes that are transcriptionally controlled by Nrf2. Additional studies are needed to understand the role of the Nrf2 pathway in controlling oxidative stress and other potential downstream biological effects.

Ying-Hsuan Lin, Maiko Arashiro, Elizabeth Martin, Yuzhi Chen, Zhenfa Zhang, Kenneth G. Sexton, Avram Gold, Ilona Jaspers, Rebecca C. Fry, and Jason D. Surratt. Isoprene-Derived Secondary Organic Aerosol Induces the Expression of Oxidative Stress Response Genes in Human Lung Cells. Environ. Sci. Technol. Lett., 2016, 3 (6), pp 250–254

Amanda J. Kramer, Weruka Rattanavaraha, Zhenfa Zhang, Avram Gold, Jason D. Surratt, Ying-Hsuan Lin. Assessing the oxidative potential of isoprene-derived epoxides and secondary organic aerosol. Atmospheric Environment, Volume 130, April 2016, Pages 211–218

Arashiro, M., Lin, Y.-H., Sexton, K.G., Zhang, Z., Jaspers, I., Fry, R.C., Vizuete, W.G., Gold, A., and Surratt, J.D. In vitro exposure to isoprene-derived secondary organic aerosol by direct deposition and its effects on COX-2 and IL-8 gene expression, Atmos. Chem. Phys., 16, 14079-14090, 2016

Lin YH, Arashiro M, Clapp PW, Cui T, Sexton KG, Vizuete W, Gold A, Jaspers IJ, Fry RC, Surratt JD. 2017. Gene expression profiling in human lung cells exposed to isoprene-derived secondary organic aerosol. Environ Sci Technol, 51(14):8166-8175.

Arashiro M, Lin YH, Zhang Z, Sexton KG, Gold, A, Jasper IJ, Fry RC, Surratt JD. 2017. Effect of secondary organic aerosol from isoprene-derived hydroxyhydroperoxides on the expression of oxidative stress response genes in human bronchial epithelial cells. Envrion Sci: Processes Impacts, doi:10.1039/C7EM00439G.


Poster by Surratt et al, 2017 HEI Annual Conference

Other News

Jason Surratt also received the following awards:

James J. Morgan ES&T Early Career Award Lectureship

Philip and Ruth Hettleman Prize for Artistic and Scholarly Achievement by Young Faculty