PMID- 12388200
OWN - NLM
STAT- MEDLINE
DCOM- 20030310
LR  - 20161124
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 284
IP  - 3
DP  - 2003 Mar
TI  - Cytokines induce HIF-1 DNA binding and the expression of HIF-1-dependent genes in 
      cultured rat enterocytes.
PG  - G373-84
AB  - Cellular adaptation to hypoxia depends, in part, on the transcription factor 
      hypoxia-inducible factor-1 (HIF-1). Normoxic cells exposed to an inflammatory 
      milieu often manifest phenotypic changes, such as increased glycolysis, that are 
      reminiscent of those observed in hypoxic cells. Accordingly, we investigated the 
      effects of cytomix, a mixture containing IFN-gamma, TNF, and IL-1beta on the 
      expression of HIF-1-dependent proteins under normoxic and hypoxic conditions. 
      Incubation of intestine-derived epithelial cells (IEC-6) under 1% O(2) increased 
      HIF-1 DNA binding and expression of aldolase A, enolase-1, and VEGF mRNA. 
      Incubation of normoxic cells with cytomix for 48 h also markedly increased HIF-1 
      DNA binding and expression of mRNAs for these proteins. Incubation of hypoxic 
      cells with cytomix did not inhibit HIF-1 DNA binding or upregulation of 
      HIF-1-dependent genes in response to hypoxia. Neither cytomix nor hypoxia 
      increased steady-state levels of HIF-1alpha mRNA. Incubation of IEC-6 cells with 
      cytomix induced nitric oxide (NO.) biosynthesis, which was blocked if the 
      cultures contained l-N(G)-(1-iminoethyl)lysine hydrochloride (l-NIL). Treatment 
      with l-NIL, however, failed to significantly alter aldolase A, enolase-1, and 
      VEGF mRNA levels in normoxic cytomix-treated cells. Proinflammatory cytokines 
      activate the HIF-1 pathway and increase expression of glycolytic genes in 
      nontransformed rat intestinal epithelial cells, largely through an 
      NO.-independent mechanism.
FAU - Scharte, Marion
AU  - Scharte M
AD  - Klinik und Poliklinik fur Anasthesiologie und Operative Intensivmedizin, 
      Universitatsklinikum Munster, Munster, Germany.
FAU - Han, Xiaonan
AU  - Han X
FAU - Bertges, Daniel J
AU  - Bertges DJ
FAU - Fink, Mitchell P
AU  - Fink MP
FAU - Delude, Russell L
AU  - Delude RL
LA  - eng
GR  - GM 37631/GM/NIGMS NIH HHS/United States
GR  - GM 58484/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20021002
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lymphokines)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 9007-49-2 (DNA)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Culture Media, Conditioned
MH  - Cytokines/*pharmacology
MH  - DNA/drug effects/*metabolism
MH  - DNA-Binding Proteins/biosynthesis/*genetics/*metabolism
MH  - Endothelial Growth Factors/biosynthesis
MH  - Enterocytes/drug effects/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/drug effects/metabolism
MH  - Fructose-Bisphosphate Aldolase/biosynthesis
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Glucose/metabolism
MH  - Hypoxia/metabolism
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Indicators and Reagents
MH  - Intercellular Signaling Peptides and Proteins/biosynthesis
MH  - Lactic Acid/biosynthesis
MH  - Lymphokines/biosynthesis
MH  - Nitrates/metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors
MH  - Nitric Oxide Synthase Type III
MH  - Nitrites/metabolism
MH  - Nuclear Proteins/biosynthesis/*genetics/*metabolism
MH  - Phosphopyruvate Hydratase/biosynthesis
MH  - RNA, Messenger/biosynthesis/isolation & purification
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Transcription Factors
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2002/10/22 04:00
MHDA- 2003/03/11 04:00
CRDT- 2002/10/22 04:00
PHST- 2002/10/22 04:00 [pubmed]
PHST- 2003/03/11 04:00 [medline]
PHST- 2002/10/22 04:00 [entrez]
AID - 00076.2002 [pii]
AID - 10.1152/ajpgi.00076.2002 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2003 Mar;284(3):G373-84. doi: 
      10.1152/ajpgi.00076.2002. Epub 2002 Oct 2.