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A systemic approach to identify signaling pathways activated during short-term exposure to traffic-related urban air pollution from human blood

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Abstract

The molecular mechanisms that promote pathologic alterations in human physiology mediated by short-term exposure to traffic pollutants remains not well understood. This work was to develop mechanistic networks to determine which specific pathways are activated by real-world exposures of traffic-related air pollution (TRAP) during rest and moderate physical activity (PA). A controlled crossover study to compare whole blood gene expression pre and post short-term exposure to high and low of TRAP was performed together with systems biology analysis. Twenty-eight healthy volunteers aged between 21 and 53 years were recruited. These subjects were exposed during 2 h to different pollution levels (high and low TRAP levels), while either cycling or resting. Global transcriptome profile of each condition was performed from human whole blood samples. Microarrays analysis was performed to obtain differential expressed genes (DEG) to be used as initial input for GeneMANIA software to obtain protein-protein (PPI) networks. Two networks were found reflecting high or low TRAP levels, which shared only 5.6 and 15.5% of its nodes, suggesting specific cell signaling pathways being activated in each environmental condition. However, gene ontology analysis of each PPI network suggests that each level of TRAP regulate common members of NF-κB signaling pathway. Our work provides the first approach describing mechanistic networks to understand TRAP effects on a system level.

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Authors and Affiliations

  1. Passo Fundo University (UPF), Passo Fundo, Rio Grande do Sul, Brazil

    José Eduardo Vargas

  2. Infant Center, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil

    José Eduardo Vargas

  3. ISGlobal, Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain

    Nadine Kubesch, Carles Hernandéz-Ferrer, Glória Carrasco-Turigas, Mariona Bustamante, Mark Nieuwenhuijsen & Juan R. González

  4. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    Nadine Kubesch, Carles Hernandéz-Ferrer, Glória Carrasco-Turigas, Mariona Bustamante, Mark Nieuwenhuijsen & Juan R. González

  5. Centre for Epidemiology and Screening, University of Copenhagen, Copenhagen, Denmark

    Nadine Kubesch

  6. Boston Children’s Hospital, Boston, USA

    Carles Hernandéz-Ferrer

  7. Centro de Investigación Biomédica en Red de Epidemiología y Salud, Pública (CIBERESP), Barcelona, Spain

    Mark Nieuwenhuijsen & Juan R. González

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  1. José Eduardo Vargas
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  2. Nadine Kubesch
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  3. Carles Hernandéz-Ferrer
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  4. Glória Carrasco-Turigas
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  7. Juan R. González
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Corresponding authors

Correspondence to José Eduardo Vargas or Juan R. González.

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The Institut Municipal d’Investigació Mèdica (IMIM) Ethics Review Committee approved the model of this study. All the volunteers signed a consent form before participating in this research.

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The authors declare that they have no conflict of interest.

Additional information

Responsible editor: Philippe Garrigues

Electronic supplementary material

Supplementary figure 1

All PPI networks obtained after meta-analysis of microarrays data. These networks were obtained from peripheral blood samples of adults exposed to low and high traffic-related air pollution exposures during moderate physical activity. (PNG 457 kb)

High resolution image (TIF 2602 kb)

Supplementary figure 2

ClueGO results of LE and HE PPI networks. These networks are created with Cohen’s kappa statistics, reflecting similarity between biological terms based on the similarity of their associated genes. A- Result derived from clustered LE PPI network. Networks derived from ClueGO analysis of unclustered LE and HE PPI networks, B and C respectively. (PNG 1231 kb)

High resolution image (TIF 3190 kb)

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Vargas, J.E., Kubesch, N., Hernandéz-Ferrer, C. et al. A systemic approach to identify signaling pathways activated during short-term exposure to traffic-related urban air pollution from human blood. Environ Sci Pollut Res 25, 29572–29583 (2018). https://doi.org/10.1007/s11356-018-3009-8

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