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.