The two C/EBP isoforms, IL6DBP/NFIL6 and CEBP6δ/NFIL63, are induced by IL6β to promote acute phase gene transcription via different mechanisms

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Abstract
The promoter regions of three IL-6 Inducible genes, hemopexin (Hpx), haptoglobin (Hp) and C-reactive protein (CRP) contain cs-acting IL-6 responsive elements (IL-6RE) which are necessary and sufficient to induce IL-6 transcription activation. Transcription factors of the CEBP family interact with IL-6REs. Among these, IL-6DBP NF-IL6 plays a key role in IL-6 signal transduction because its frans-activation potential Is induced by IL-6 in the human hepatoma cell line Hep3B. We show here that a different CEBP related factor, C/EBP/ NF L6β, is the major IL-6 induced protein interacting with IL-6REs in the nuclei of Hep3B cells. In contrast to IL-6DBPδNF/-IL6, whose activity in Hep3B cells is modulated by IL-6 via a post translational mechanism, CEBδPS/NF-IL6β is transcriptionally induced by IL-6. Another contrasting feature is that the CEBP6 cDNA transfected In Hep3B cells activates transcription from an IL-6RE synthetic promoter in a constitutive manner which is not further enhanced by IL-6. Therefore, in Hep3B cells, two distinct members of the CEBP family are recruited In the IL-6 signal transductlon pathway via different mechanisms.