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Recent studies in our laboratory have shown that apo C-III promoter activity and in vivo mRNA levels decreased when HepG2 cells were treated with IL-1 or IL-6. We have mapped the corresponding response element in the proximal promoter region of apo C-III and found that it binds NFëB family members (p65, p50, c-rel), as well as C/EBPá, C/EBPâ, and C/EBPç in a mutually exclusive manner. These factors dramatically activate transcription of different mutant promoter constructs in which the interaction of HNF-4 with upstream enhancer binding factors are disrupted. On the other hand, in the context of the wild type promoter they induce a negative response. Our results suggest that the overall inhibition of apo C-III expression during the acute phase reaction is mediated by cytokine-induced positive factors through the disruption of a stronger transcriptionally active complex, which operates under normal physiological conditions.
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