title: AhR- and NF-κB-dependent induction of interleukin-6 by co-exposure to the environmental contaminant benzanthracene and the cytokine tumor necrosis factor-α in human mammary MCF-7 cells.
abstract: Co-exposure to environmental polycyclic aromatic hydrocarbons (PAHs) and interleukin (IL)-1β induces expression of the tumor-promoting cytokine IL-6 in cancer cells. The present study was designed to determine whether such an IL-6 up-regulation also occurs in response to co-treatment by PAHs and tumor necrosis factor (TNF)-α, an inflammatory cytokine commonly found in tumor microenvironment. Co-exposure to the prototypical PAH benzanthracene (BZA) and TNF-α was found to markedly induce mRNA expression and secretion of IL-6 in human breast cancer cells MCF-7, whereas exposure to either BZA or TNF-α alone was without significant effect. Co-treatment by BZA and TNF-α-containing conditioned media from human inflammatory macrophages similarly up-regulated IL-6 expression in MCF-7 cells. BZA/TNF-α-mediated IL-6 induction in MCF-7 cells was counteracted by silencing aryl hydrocarbon receptor (AhR), known to mediates most of PAH effects. IL-6 up-regulation was moreover associated with NF-κB activation and was abolished by using chemical NF-κB inhibitors or knocking-down expression of the p65/RelA NF-κB subunit. Taken together, these data indicate that co-exposure to BZA/TNF-α induces IL-6 expression by AhR- and NF-κB-dependent pathways in MCF-7 cancer cells. This regulation of IL-6 by environmental PAHs, that is dependent of inflammatory cytokine microenvironment, may contribute to the well-known carcinogenic properties of these organic pollutants.
authors: Institut de Recherche sur la Santé, l'Environnement et le Travail (IRSET)/INSERM U1085, Université de Rennes 1, 2 avenue du Pr Leon Bernard, 35043 Rennes Cedex, France.
authors: Elise
authors: E
authors: Kolasa
authors: Noemie
authors: N
authors: Houlbert
authors: Patrick
authors: P
authors: Balaguer
authors: Olivier
authors: O
authors: Fardel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D061986:MCF-7 Cells; D008264:Macrophages / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001551:Benz(a)Anthracenes; D004785:Environmental Pollutants; D015850:Interleukin-6; C099942:NEDD9 protein, human; D016328:NF-kappa B; D010750:Phosphoproteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C030935:benz(a)anthracene