PMID- 10477681
OWN - NLM
STAT- MEDLINE
DCOM- 19990929
LR  - 20220408
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 5
DP  - 1999 Sep 1
TI  - Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of 
      hypoxia-inducible factor-1.
PG  - 1561-7
AB  - The rate of transcription of several genes encoding proteins involved in O(2) and 
      energy homeostasis is controlled by hypoxia-inducible factor-1 (HIF-1), a 
      heterodimeric DNA binding complex composed of alpha and beta subunits. HIF-1 is 
      considered the primary trans-acting factor for the erythropoietin (EPO) and 
      vascular endothelial growth factor (VEGF) genes. Since EPO gene expression is 
      inhibited by the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor 
      necrosis factor-alpha (TNF-alpha), while no such effect has been reported with 
      respect to the VEGF gene, we investigated the effects of IL-1beta and TNF-alpha 
      on the activation of the HIF-1 DNA-binding complex and the amount of HIF-1alpha 
      protein in human hepatoma cells in culture. Under normoxic conditions, both 
      cytokines caused a moderate activation of HIF-1 DNA binding. In hypoxia, 
      cytokines strongly increased HIF-1 activity compared with the effect of hypoxia 
      alone. Only IL-1beta increased HIF-1alpha protein levels. In transient 
      transfection experiments, HIF-1-driven reporter gene expression was augmented by 
      cytokines only under hypoxic conditions. In contrast to their effect on EPO 
      synthesis, neither IL-1beta nor TNF-alpha decreased VEGF production. The mRNA 
      levels of HIF-1alpha and VEGF were unaffected. Thus, cytokine-induced inhibition 
      of EPO production is not mediated by impairment of HIF-1 function. We propose 
      that HIF-1 may be involved in modulating gene expression during inflammation.
FAU - Hellwig-Burgel, T
AU  - Hellwig-Burgel T
AD  - Institut fur Physiologie, Medizinische Universitat zu Lubeck, Lubeck, Germany. 
      Hellwig@physio.mu-luebeck.de
FAU - Rutkowski, K
AU  - Rutkowski K
FAU - Metzen, E
AU  - Metzen E
FAU - Fandrey, J
AU  - Fandrey J
FAU - Jelkmann, W
AU  - Jelkmann W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interleukin-1)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/genetics/*metabolism
MH  - DNA/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hypoxia/genetics/metabolism
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Interleukin-1/*pharmacology
MH  - Liver Neoplasms/genetics/*metabolism
MH  - Liver Neoplasms, Experimental/genetics/*metabolism
MH  - Mice
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Protein Binding
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
EDAT- 1999/09/09 00:00
MHDA- 1999/09/09 00:01
CRDT- 1999/09/09 00:00
PHST- 1999/09/09 00:00 [pubmed]
PHST- 1999/09/09 00:01 [medline]
PHST- 1999/09/09 00:00 [entrez]
AID - S0006-4971(20)48853-6 [pii]
PST - ppublish
SO  - Blood. 1999 Sep 1;94(5):1561-7.