Upregulation of CYP1B1 expression by inflammatory cytokines is mediated by the p38 MAP kinase signal transduction pathway

0440091 - BFÚ 2015 RIV GB eng J - Článek v odborném periodiku
Šmerdová, Lenka - Svobodová, Jana - Kabátková, Markéta - Kohoutek, J. - Blažek, D. - Machala, M. - Vondráček, Jan
Upregulation of CYP1B1 expression by inflammatory cytokines is mediated by the p38 MAP kinase signal transduction pathway.
Carcinogenesis. Roč. 35, č. 11 (2014), s. 2534-2543. ISSN 0143-3334. E-ISSN 1460-2180
Grant CEP: GA ČR(CZ) GAP503/11/1227; GA ČR GA14-09979S; GA MŠMT(CZ) EE2.3.30.0030
Klíčová slova: ARYL-HYDROCARBON RECEPTOR * TUMOR-NECROSIS-FACTOR * RNA-POLYMERASE-II
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 5.334, rok: 2014

Cytochrome P450 1B1 (CYP1B1) is an enzyme that has a unique tumor-specific pattern of expression and is capable of bioactivating a wide range of carcinogenic compounds. We have reported previously that coordinated upregulation of CYP1B1 by inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and the aryl hydrocarbon receptor ligands, may increase bioactivation of promutagens, such as benzo[a]pyrene (BaP) in epithelial cells. Here, we extend those studies by describing a novel mechanism participating in the regulation of CYP1B1 expression, which involves activation of the p38 mitogen-activated protein kinase (p38) and mitogen- and stress-activated protein kinase 1 (MSKI). Using inhibitors of p38 and MSKs, as well as mouse embryonic cells derived from p38 alpha-deficient and MSK1/2 double knockout mice, we show here that TNF-alpha potentiates CYPIRI upregulation via the p38/MSK1 kinase cascade. Effects of this inflammatory cytokine on CYPIBI expression further involve the positive transcription elongation factor b (P-TEFb).
Trvalý link: http://hdl.handle.net/11104/0243231