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Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[a]pyrene

ABSTRACT: Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[a]pyrene

PROVIDER: PRJNA482396 | ENA |

REPOSITORIES: ENA

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Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[a]pyrene

Project description:Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P), are widely distributed carcinogenic and immunotoxic environmental contaminants, known to affect T lymphocytes. Despite extensive studies conducted, the molecular targets and pathways involved in their immunotoxic effects in human T lymphocytes remain unknown. Here, we analyzed the gene expression profile of primary human T lymphocytes treated with the prototypical PAH, B[a]P using a microarray-based transcriptome analysis. After a 48-h exposure to B[a]P, we identified 158 genes differentially expressed in T lymphocytes including not only genes well-known to be affected by PAHs such as the cytochromes P450 (CYP) 1A1 and 1B1, and the proto-oncogene c-KIT but also other ones not previously shown to be targeted by B[a]P such as genes encoding the gap junction beta-2 (GJB2) and beta-6 (GJB6) proteins. Functional enrichment analysis revealed that those candidates were significantly associated with the aryl hydrocarbon (AhR) and interferon (IFN) signalling pathways; it also revealed a clear alteration in essential biological functions, mainly those related to T lymphocyte recruitment. These data were confirmed by RT-qPCR assays for some selected genes such as the chemokine (C-C motif) ligand CCL3, and the cell adhesion protein like selectin L (SELL). Using functional tests in transwell migration experiments, B[a]P was shown to significantly decrease the chemokine (C-X-C motif) ligand 12 (CXCL12)-induced chemotaxis and transendothelial migration of T lymphocytes. Overall, the present study opens the way to unsuspected responsive pathway of interest, i.e., T lymphocyte migration, providing a broader understanding of the molecular basis of the immunotoxicity of PAHs.

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Cytochrome P450 Monooxygenase Mediated Metabolic Utilization of Benzo(a)pyrene by Fungi

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