Transforming growth factor-beta1 inhibits expression of selenoprotein P in cultured human liver cells.
The effect of cytokines on the expression of selenoprotein P (SeP) in the human liver cell line HepG2 was investigated. Treatment with interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha had no effect on SeP levels in culture media or on SeP mRNA expression. Conversely, Western analysis revealed a dose-dependent reduction of SeP content in culture medium after treatment with transforming growth factor (TGF)-beta1 with an 1C50 of 31 pM. Treatment with 100 pM TGF-51 for 48 h led to a decrease to 21 +/- 9% of controls. RT-PCR analysis of SeP mRNA expression demonstrated an inhibition of SeP transcription to 40+/-2% of control levels after 24 h. The expression of a luciferase reporter construct under control of the human SeP promoter was downregulated by TGF-beta1 treatment in a dose-dependent fashion indicating a transcriptional regulation of the SeP gene by TGF-beta1.
Mostert
V
V
Medical Institute of Environmental Hygiene at the Heinrich-Heine-Universität Düsseldorf, Department of Experimental Toxicology, Germany.
Dreher
I
I
Kohrle
J
J
Abel
J
J
D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051149:Selenoprotein P; D051140:Selenoproteins; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D011506:Proteins; D012333:RNA, Messenger; D051149:Selenoprotein P; D051140:Selenoproteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003513:Cycloheximide