Tumor necrosis factor-alpha modulates effects of aryl hydrocarbon receptor ligands on cell proliferation and expression of cytochrome P450 enzymes in rat liver "stem-like" cells
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P42 ES007380
NIEHS NIH HHS - United States
PubMed
17557910
DOI
10.1093/toxsci/kfm149
PII: kfm149
Knihovny.cz E-zdroje
- MeSH
- aromatické hydroxylasy genetika metabolismus MeSH
- cytochrom P-450 CYP1A1 genetika metabolismus MeSH
- cytochrom P450 CYP1B1 MeSH
- epitelové buňky účinky léků enzymologie MeSH
- fixní kombinace léků MeSH
- játra cytologie MeSH
- karcinogeny metabolismus toxicita MeSH
- kmenové buňky účinky léků enzymologie MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- lékové interakce MeSH
- ligandy MeSH
- polychlorované bifenyly metabolismus toxicita MeSH
- polychlorované dibenzodioxiny metabolismus toxicita MeSH
- potkani inbrední F344 MeSH
- proliferace buněk účinky léků MeSH
- receptory aromatických uhlovodíků účinky léků metabolismus MeSH
- regulace genové exprese enzymů účinky léků MeSH
- TNF-alfa farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- 3,4,5,3',4'-pentachlorobiphenyl MeSH Prohlížeč
- aromatické hydroxylasy MeSH
- Cyp1b1 protein, rat MeSH Prohlížeč
- cytochrom P-450 CYP1A1 MeSH
- cytochrom P450 CYP1B1 MeSH
- fixní kombinace léků MeSH
- karcinogeny MeSH
- ligandy MeSH
- polychlorované bifenyly MeSH
- polychlorované dibenzodioxiny MeSH
- receptory aromatických uhlovodíků MeSH
- TNF-alfa MeSH
Various liver diseases lead to an extensive inflammatory response and release of a number of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha). This cytokine is known to play a major role in liver regeneration as well as in carcinogenesis. We investigated possible interactions of TNF-alpha with ligands of the aryl hydrocarbon receptor (AhR) and known liver carcinogens, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and coplanar 3,3',4,4',5-pentachlorobiphenyl (PCB 126). These compounds have been previously found to disrupt cell cycle control in contact-inhibited rat liver WB-F344 cells, an in vitro model of adult liver progenitor cells. TNF-alpha itself had no significant effect on the proliferation/apoptosis ratio in the WB-F344 cell line. However, it significantly potentiated proliferative effects of low picomolar range doses of both TCDD and PCB 126, leading to an increase in cell numbers, as well as an increased percentage of cells entering the S-phase of the cell cycle. The combination of TNF-alpha with low concentrations of AhR ligands increased both messenger RNA (mRNA) and protein levels of cyclin A, a principle cyclin involved in disruption of contact inhibition. TNF-alpha temporarily inhibited AhR-dependent induction of cytochrome P450 1A1 (CYP1A1). In contrast, TNF-alpha significantly enhanced induction of CYP1B1 at both mRNA and protein levels, by a mechanism, which was independent of nuclear factor-kappaB activation. These results suggest that TNF-alpha can significantly amplify effects of AhR ligands on deregulation of cell proliferation control, as well as on expression of CYP1B1, which is involved in metabolic activation of a number of mutagenic compounds.
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