Repression of apoC-III gene expression by TNFalpha involves C/EBPdelta/NF-IL6beta via an IL-1 independent pathway.
Apolipoproteins A-II and C-III, which participate in the control of cholesterolemia and triglyceridemia, are negative acute phase proteins. Treatment of HepG2 cells with TNFalpha showed that apoA-II and apoC-III mRNA levels were decreased. Using transient transfection, we found that apoC-III gene expression is controlled at the transcriptional level. By competition and supershift experiments, we demonstrate that TNFalpha-induced complexes were related to C/EBPdelta/NF-IL6beta and p50 and that overexpression of C/EBPdelta was able to reproduce the inhibitory effect of TNFalpha on the apoC-III promoter. RT-PCR failed to detect the IL-1 transcript in TNFalpha-treated HepG2 cells, suggesting that activation of C/EBPdelta by TNFalpha is not related to the IL-1-signalling pathway.
Lacorte
J M
JM
CJF INSERM 9508 and URA-CNRS 1283, Paris, France.
Beigneux
A
A
Parant
M
M
Chambaz
J
J
D016633:Apolipoprotein A-II / Q000235:genetics / Q000378:metabolism; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics* / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D006528:Carcinoma, Hepatocellular; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016633:Apolipoprotein A-II; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D051743:CCAAT-Enhancer-Binding Protein-delta; D015500:Chloramphenicol O-Acetyltransferase