TY - JOUR
T1 - Erythropoietin production: Molecular mechanisms of the antagonistic actions of cyclic adenosine monophosphate and interleukin-1
AU - Batmunkh, Chimedtseren
AU - Krajewski, Jochen
AU - Jelkmann, Wolfgang
AU - Hellwig-Bürgel, Thomas
N1 - Funding Information:
We are grateful to Ms. Gabriele Huck for excellent technical assistance. Financial support was provided by the German Research Society (DFG, GRK-288) and the Mongolian Academy of Sciences.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/5/29
Y1 - 2006/5/29
N2 - 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-κB, 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-κB, which is a likely suppressor of the Epo promoter. Treatment of the cells with dibutyryl-cAMP (Bt2-cAMP) inhibited the activation of NF-κB 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-κB is probably the primary transcription factor by which cAMP counteracts the inhibition of Epo gene expression by IL-1.
AB - 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-κB, 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-κB, which is a likely suppressor of the Epo promoter. Treatment of the cells with dibutyryl-cAMP (Bt2-cAMP) inhibited the activation of NF-κB 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-κB is probably the primary transcription factor by which cAMP counteracts the inhibition of Epo gene expression by IL-1.
UR - http://www.scopus.com/inward/record.url?scp=33646560932&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2006.04.069
DO - 10.1016/j.febslet.2006.04.069
M3 - Journal articles
C2 - 16684536
AN - SCOPUS:33646560932
SN - 0014-5793
VL - 580
SP - 3153
EP - 3160
JO - FEBS Letters
JF - FEBS Letters
IS - 13
ER -