Involvement of CCAAT/enhancer-binding protein alpha in haptoglobin gene expression by all-trans-retinoic acid.
Several acute-phase plasma proteins, including haptoglobin (Hp), are induced in the liver in response to inflammation. Recently, we found that Hp gene expression is up-regulated by all-trans-retinoic acid (ATRA) in the extrahepatic monocytic cell line, THP-1. To investigate the molecular mechanism underlying ATRA-induced Hp gene expression, we analyzed the induction of transcription factor CCAAT/enhancer-binding protein (C/EBP) isoforms in ATRA-stimulated THP-1 cells and their binding to the Hp promoter. Western blot analysis showed that treatment with ATRA increased C/EBPalpha and beta expression, but decreased that of C/EBPdelta. Electrophoretic mobility shift and supershift assays demonstrated that only C/EBPalpha of the C/EBP isoforms bound to the C/EBP DNA-binding sites in the Hp promoter. Furthermore, when ATRA-dependent Hp induction was inhibited by sodium butyrate or auranofin, induction of C/EBPalpha, but not C/EBPbeta, was also diminished. These results suggest that C/EBPalpha is involved in the activation of Hp gene expression by ATRA in human monocytic cells.
Lee
Il-Ha
IH
Department of Natural Sciences, Chemistry Section, College of Medicine, Catholic University of Korea, 505 Banpo-Dong, Socho-Gu, Seoul 137-701, Republic of Korea.
Lee
Jeong-Hwa
JH
Lee
Myung-Jae
MJ
Lee
Soo-Young
SY
Kim
In-Sook
IS
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000502:physiology*; D002460:Cell Line; D006242:Haptoglobins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000893:Anti-Inflammatory Agents; D022763:CCAAT-Enhancer-Binding Protein-alpha; D006242:Haptoglobins; D015850:Interleukin-6; D020033:Protein Isoforms; D012333:RNA, Messenger; D014212:Tretinoin