The two C/EBP isoforms, IL-6DBP/NF-IL6 and C/EBP delta/NF-IL6 beta, are induced by IL-6 to promote acute phase gene transcription via different mechanisms.
The promoter regions of three IL-6 inducible genes, hemopexin (Hpx), haptoglobin (Hp) and C-reactive protein (CRP) contain cis-acting IL-6 responsive elements (IL-6REs) which are necessary and sufficient to induce IL-6 transcription activation. Transcription factors of the C/EBP family interact with IL-6REs. Among these, IL-6DBP/NF-IL6 plays a key role in IL-6 signal transduction because its trans-activation potential is induced by IL-6 in the human hepatoma cell line Hep3B. We show here that a different C/EBP-related factor, C/EBP delta/NF-IL6 beta, is the major IL-6 induced protein interacting with IL-6REs in the nuclei of Hep3B cells. In contrast to IL-6DBP/NF-IL6, whose activity in Hep3B cells is modulated by IL-6 via a post-translational mechanism, C/EBP delta/NF-IL6 beta is transcriptionally induced by IL-6. Another contrasting feature is that the C/EBP delta 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 C/EBP family are recruited in the IL-6 signal transduction pathway via different mechanisms.
Ramji
D P
DP
Istituto di Ricerche di Biologia Molecolare (IRBM) P. Angeletti, Pomezia, Rome, Italy.
Vitelli
A
A
Tronche
F
F
Cortese
R
R
Ciliberto
G
G
D000209:Acute-Phase Proteins / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D006528:Carcinoma, Hepatocellular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D004247:DNA