Dataset Information

Genome-Wide Transcriptional and Functional Analysis of Human T Lymphocytes Treated with Benzo[?]pyrene.

ABSTRACT: Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environmental contaminants, known to affect T lymphocytes. However, 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, benzo[?]pyrene (B[?]P), using a microarray-based transcriptome analysis. After a 48 h exposure to B[?]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, but also others not previously shown to be targeted by B[?]P such as genes encoding the gap junction beta (GJB)-2 and 6 proteins. Functional enrichment analysis revealed that these candidates were significantly associated with the aryl hydrocarbon (AhR) and interferon (IFN) signaling pathways; a marked alteration in T lymphocyte recruitment was also observed. Using functional tests in transwell migration experiments, B[?]P was then shown to significantly decrease the chemokine (C-X-C motif) ligand 12-induced chemotaxis and transendothelial migration of T lymphocytes. In total, this study opens the way to unsuspected responsive pathway of interest, i.e., T lymphocyte migration, thus providing a more thorough understanding of the molecular basis of the immunotoxicity of PAHs.

SUBMITTER: Liamin M

PROVIDER: S-EPMC6274903 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Genome-Wide Transcriptional and Functional Analysis of Human T Lymphocytes Treated with Benzo[α]pyrene.

Liamin Marie M Le Mentec Hélène H Evrard Bertrand B Huc Laurence L Chalmel Frédéric F Boutet-Robinet Elisa E Le Ferrec Eric E Sparfel Lydie L

International journal of molecular sciences 20181117 11

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environmental contaminants, known to affect T lymphocytes. However, 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, benzo[α]pyrene (B[α]P), using a microarray-based transcriptome analysis. After a 48 h exposure to B[α]P, we identified 158 g ...[more]

PMID: 30453624

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Project description:Animals have developed extensive mechanisms of response to xenobiotic chemical attacks. Although recent genome surveys have suggested a broad conservation of the chemical defensome across metazoans, global gene expression responses to xenobiotics are not known in most invertebrates. Here, using high density tiling arrays with over 2 million probes, we explored genome-wide gene expression in the tunicate Oikopleura dioica in response to two model xenobiotic chemicals – the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) the pharmaceutical compound Clofibrate (Clo). The genotoxic compound BaP induced xenobiotic biotransformation and oxidative stress responsive genes, as in vertebrates. Notable exceptions were genes of the aryl hydrocarbon receptor (AhR) signaling pathway. Clo also affected the expression of many biotransformation genes and markedly repressed genes involved in energy metabolism and muscle contraction pathways. Oikopleura appears to have basic defensome toolkit consisting of phase I, phase II and phase III biotransformation genes. Exposure of about 130 four-days-old animals in 1L seawater in glass beakers. Pooled animals used, no replicates. DMSO Treatments: -Clofibrate (Clo) (Sigma-Aldrich, St. Louis, MO): 1 µM and 5 µM. -Benzo[a]pyrene (BaP (Sigma-Aldrich): 0.2 µM and 1 µM - Controls received 1 ml Dimethyl sulfoxide (DMSO). -The animals kept at room temperature and harvested after 10 hrs and frozen. -Total RNA was isolated from the pooled animals using the RNeasy Mini Kit according to manufacturer’s protocols (QIAGEN, Hilden, Germany). - 5 µg total RNA was converted to dscDNA using SuperScript Double-Stranded cDNA Synthesis Kit (Invitrogen, Carlsbad, CA), and dscDNA samples were submitted for microarray analysis. BaP and Clo treated samples were labeled using Cy3-coupled random nonamers and DMSO controls were labeled using Cy5-coupled random nonamers. Total 4 hybridizations for the 8 samples (single hybridization for each treatment and DMSO control pair), no replicates.

Dataset Information

Genome-Wide Transcriptional and Functional Analysis of Human T Lymphocytes Treated with Benzo[?]pyrene.

Publications

Genome-Wide Transcriptional and Functional Analysis of Human T Lymphocytes Treated with Benzo[<i>α</i>]pyrene.

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