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@article{1220120,
author = {Kabátková, Markéta and Svobodová, Jana and Pěnčíková, Kateřina and Mohatad, Dilshad and Šmerdová, Lenka and Kozubík, Alois and Machala, Miroslav and Vondráček, Jan},
article_location = {CLARE},
article_number = {1},
doi = {http://dx.doi.org/10.1016/j.toxlet.2014.09.023},
keywords = {PAHs; Inflammation; Cell proliferation; Gap junctions; Aryl hydrocarbon receptor},
language = {eng},
issn = {0378-4274},
journal = {Toxicology Letters},
title = {Interactive effects of inflammatory cytokine and abundant low-molecular-weight PAHs on inhibition of gap junctional intercellular communication, disruption of cell proliferation control, and the AhR-dependent transcription},
url = {http://www.sciencedirect.com/science/article/pii/S0378427414013575},
volume = {232},
year = {2015}
}
TY - JOUR
ID - 1220120
AU - Kabátková, Markéta - Svobodová, Jana - Pěnčíková, Kateřina - Mohatad, Dilshad - Šmerdová, Lenka - Kozubík, Alois - Machala, Miroslav - Vondráček, Jan
PY - 2015
TI - Interactive effects of inflammatory cytokine and abundant low-molecular-weight PAHs on inhibition of gap junctional intercellular communication, disruption of cell proliferation control, and the AhR-dependent transcription
JF - Toxicology Letters
VL - 232
IS - 1
SP - 113-121
EP - 113-121
PB - Elsevier
SN - 03784274
KW - PAHs
KW - Inflammation
KW - Cell proliferation
KW - Gap junctions
KW - Aryl hydrocarbon receptor
UR - http://www.sciencedirect.com/science/article/pii/S0378427414013575
N2 - Polycyclic aromatic hydrocarbons (PAHs) with lower molecular weight exhibit lesser genotoxicity and carcinogenicity than highly carcinogenic PAHs with a higher number of benzene rings. Nevertheless, they elicit specific effects linked with tumor promotion, such as acute inhibition of gap junctional intercellular communication (GJIC). Although inflammatory reaction may alter bioactivation and toxicity of carcinogenic PAHs, little is known about the impact of pro-inflammatory cytokines on toxic effects of the low-molecular-weight PAHs. Here, we investigated the impact of a pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), on the effects associated with tumor promotion and with induction of the aryl hydrocarbon receptor (AhR)-dependent gene expression in rat liver epithelial cells. We found that a prolonged incubation with TNF-alpha induced a down-regulation of GJIC, associated with reduced expression of connexin 43 (Cx43), a major connexin isoform found in liver epithelial cells. The Cx43 down-regulation was partly mediated by the activity of the mitogen-activated protein (MAP) p38 kinase. Independently of GJIC modulation, or p38 activation, TNF-alpha potentiated the AhR-dependent proliferative effect of a model low-molecular-weight PAH, fluoranthene, on contact-inhibited cells. In contrast, this pro-inflammatory cytokine repressed the fluoranthene-induced expression of a majority of model AhR gene targets, such as Cyp1a1, Ahrr or Tiparp. The results of the present study indicate that inflammatory reaction may differentially modulate various toxic effects of low-molecular-weight PAHs; the exposure to pro-inflammatory cytokines may both strengthen (inhibition of GJIC, disruption of contact inhibition) and repress (expression of a majority of AhR-dependent genes) their impact on toxic endpoints associated with carcinogenesis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
ER -
KABÁTKOVÁ, Markéta, Jana SVOBODOVÁ, Kateřina PĚNČÍKOVÁ, Dilshad MOHATAD, Lenka ŠMERDOVÁ, Alois KOZUBÍK, Miroslav MACHALA and Jan VONDRÁČEK. Interactive effects of inflammatory cytokine and abundant low-molecular-weight PAHs on inhibition of gap junctional intercellular communication, disruption of cell proliferation control, and the AhR-dependent transcription. \textit{Toxicology Letters}. CLARE: Elsevier, 2015, vol.~232, No~1, p.~113-121. ISSN~0378-4274. Available from: https://dx.doi.org/10.1016/j.toxlet.2014.09.023.
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