PMID- 16533170
OWN - NLM
STAT- MEDLINE
DCOM- 20060612
LR  - 20220408
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 396
IP  - 3
DP  - 2006 Jun 15
TI  - Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via 
      p44/42 MAPK and NF-kappaB.
PG  - 517-27
AB  - Inflammatory mediators activate the transcriptional complex HIF-1 
      (hypoxia-inducible factor-1), the key regulator of hypoxia-induced gene 
      expression. Here we report that bacterial LPS (lipopolysaccharide) induces 
      HIF-1alpha mRNA expression and HIF-1alpha protein accumulation in human monocytes 
      as well as in non-differentiated and differentiated cells of the human monocytic 
      cell line THP-1 under normoxic conditions. LPS and hypoxia synergistically 
      activated HIF-1. Whereas LPS increased HIF-1alpha mRNA expression through 
      activation of a NF-kappaB (nuclear factor kappaB) site in the promoter of the 
      HIF-1alpha gene, hypoxia post-translationally stabilized HIF-1alpha protein. 
      HIF-1alpha activation was followed by increased expression of the HIF-1 target 
      gene encoding ADM (adrenomedullin). Knocking down HIF-1alpha by RNA interference 
      significantly decreased ADM expression, which underlines the importance of HIF-1 
      for the LPS-induced ADM expression in normoxia. Simultaneously with HIF-1 
      activation, an increase in p44/42 MAPK (mitogen-activated protein kinase) 
      phosphorylation was observed after incubation with LPS. In cells pretreated with 
      the p44/42 MAPK inhibitor PD 98059 or with RNAi (interfering RNA) directed 
      against p44/42 MAPK, LPS-induced HIF-1alpha accumulation and ADM expression were 
      significantly decreased. From these results we conclude that LPS critically 
      involves the p44/42 MAPK and NF-kappaB pathway in the activation of HIF-1, which 
      is an important transcription factor for LPS-induced ADM expression.
FAU - Frede, Stilla
AU  - Frede S
AD  - Institut fur Physiologie, Universitat Duisburg-Essen Hufelandstrasse 55, D-45122 
      Essen, Federal Republic of Germany.
FAU - Stockmann, Christian
AU  - Stockmann C
FAU - Freitag, Patricia
AU  - Freitag P
FAU - Fandrey, Joachim
AU  - Fandrey J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Flavonoids)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptides)
RN  - 148498-78-6 (Adrenomedullin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Adrenomedullin
MH  - Cell Line
MH  - Electrophoretic Mobility Shift Assay
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Hypoxia/physiopathology
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis
MH  - Lipopolysaccharide Receptors/biosynthesis
MH  - Lipopolysaccharides/*pharmacology
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism
MH  - Monocytes/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Peptides/metabolism
MH  - RNA Interference
PMC - PMC1482811
EDAT- 2006/03/15 09:00
MHDA- 2006/06/13 09:00
PMCR- 2006/12/15
CRDT- 2006/03/15 09:00
PHST- 2006/03/15 09:00 [pubmed]
PHST- 2006/06/13 09:00 [medline]
PHST- 2006/03/15 09:00 [entrez]
PHST- 2006/12/15 00:00 [pmc-release]
AID - BJ20051839 [pii]
AID - bj3960517 [pii]
AID - 10.1042/BJ20051839 [doi]
PST - ppublish
SO  - Biochem J. 2006 Jun 15;396(3):517-27. doi: 10.1042/BJ20051839.