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

0440992 - BFÚ 2015 RIV IE eng J - Článek v odborném periodiku
Kabátková, Markéta - Svobodová, Jana - Pěnčíková, K. - Mohatad, D.S. - Šmerdová, Lenka - Kozubík, Alois - Machala, M. - Vondráček, Jan
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.
Toxicology Letters. Roč. 232, č. 1 (2015), s. 113-121. ISSN 0378-4274. E-ISSN 1879-3169
Grant CEP: GA ČR(CZ) GAP503/11/1227; GA ČR(CZ) GA13-07711S
Institucionální podpora: RVO:68081707
Klíčová slova: PAHs * Inflammation * Cell proliferation
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 3.522, rok: 2015

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.
Trvalý link: http://hdl.handle.net/11104/0244065