REPRESSION OF APOC-III GENE-EXPRESSION BY TNF-ALPHA INVOLVES C EBP-DELTA/NF-IL6-BETA VIA AN IL-1 INDEPENDENT PATHWAY/

Apolipoproteins A-II and C-III, which participate in the control of ch olesterolemia and triglyceridemia, are negative acute phase proteins, Treatment of HepG2 cells with TNF alpha showed that apoA-II and apoC-I II mRNA levels were decreased, Using transient transfection, we found that apoC-III gene expression is controlled at the transcriptional lev el. By competition and supershift experiments, we demonstrate that TNF alpha-induced complexes mere related to C/EBP delta/NF-IL6 beta and p 50 and that overexpression of C/EBP delta was able to reproduce the in hibitory effect of TNF alpha on the apoC-III promoter, RT-PCR failed t o detect the IL-1 transcript in TNF alpha-treated HepG2 cells, suggest ing that activation of C/EBP delta by TNF alpha is not related to the IL-1-signalling pathway. (C) 1997 Federation of European Biochemical S ocieties.