Erythropoietin Production: Molecular Mechanisms of the Antagonistic Actions of Cyclic Adenosine Monophosphate and Interleukin-1.
From: Institute of Physiology, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany.
FEBS letters
- Publish Date: May 2006
- ISSN: 0014-5793
- Volume: 580
- Issue: 13
- Pages: 3153-60
- Medium: Print
- Language: English
- Citation (JAMA): Batmunkh Chimedtseren, Krajewski Jochen, Jelkmann Wolfgang, et al. Erythropoietin Production: Molecular Mechanisms of the Antagonistic Actions of Cyclic Adenosine Monophosphate and Interleukin-1.. FEBS Lett. May 2006;580:3153-60
Abstract
Erythropoietin (Epo) mRNA expression is suppressed by interleukin 1 (IL-1). Cyclic adenosine monophosphate (cAMP) can increase Epo mRNA and Epo protein levels in IL-1 treated HepG2 cells to some extent. To identify molecular mechanisms of this reaction we investigated three transcription factors (NF-kappaB, GATA-2 and HIF-1) that control the Epo gene. Western blot analyses and electrophoretic mobility shift assays (EMSAs) revealed that IL-1 strongly activated NF-kappaB, which is a likely suppressor of the Epo promoter. Treatment of the cells with dibutyryl-cAMP (Bt2-cAMP) inhibited the activation of NF-kappaB by IL-1. Bt2-cAMP increased GATA-2 DNA binding. Since GATA-2 is a suppressor of the Epo promoter, GATA-2 activation was unlikely to cause the increase of Epo mRNA expression in IL-1 treated cells. Furthermore, Western blots, EMSAs and reporter gene studies showed that Bt2-cAMP was without effect on the hypoxia-inducible transcription factor HIF-1. Thus, NF-kappaB is probably the primary transcription factor by which cAMP counteracts the inhibition of Epo gene expression by IL-1.
Mesh Headings (Keywords): Blotting, Western, Cells, Cultured, Cyclic AMP, Cyclic CMP, Electrophoretic Mobility Shift Assay, Erythropoietin, GATA2 Transcription Factor, Gene Expression Regulation, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Interleukin-1, NF-kappa B, Promoter Regions (Genetics), RNA, Messenger
Check for Full Text / PubMed Unique Identifier (PMID): 16684536
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