作者: Lydie Sparfel , Marie-Laure Pinel-Marie , Magali Boize , Serge Koscielny , Sophie Desmots
关键词:
摘要: Polycyclic aromatic hydrocarbons (PAHs) are widely distributed immunotoxic and carcinogenic environmental contaminants, known to affect macrophages. In order identify their molecular targets in such cells, we have analyzed gene expression profile of primary human macrophages treated by the prototypical PAH benzo(a)pyrene (BaP), using pangenomic oligonucleotides microarrays. Exposure BaP for 8 24 h resulted 96 1100 genes, differentially expressed at least a twofold change factor, respectively. Some these targets, including chemokine receptor CXCR5, G protein-coupled 35 (GPR35), Ras regulator RASAL1, not been previously shown be affected PAHs, contrast others, as interleukin-1beta aryl hydrocarbon (AhR) repressor. These BaP-mediated regulations were fully validated reverse transcription-quantitative polymerase chain reaction assays some selected genes. Their bioinformatic analysis indicated that biological functions linked immunity, inflammation, cell death among most AhR p53 signaling pathways significant canonical activated PAH. implications moreover confirmed prevention BaP-related upregulation target genes silencing or use pifithrin-alpha, an inhibitor bioactivation-related DNA damage/p53 pathways. Overall, data, through identifying targeted PAHs macrophages, may contribute better understand basis immunotoxicity contaminants.