PMID- 23362200
OWN - NLM
STAT- MEDLINE
DCOM- 20130904
LR  - 20161125
IS  - 1437-4315 (Electronic)
IS  - 1431-6730 (Linking)
VI  - 394
IP  - 4
DP  - 2013 Apr
TI  - Role of hypoxia inducible factor-1alpha for interferon synthesis in mouse dendritic 
      cells.
PG  - 495-505
LID - 10.1515/hsz-2012-0320 [doi]
AB  - Dendritic cells (DCs) are an important link between innate and adaptive immunity. 
      DCs get activated in inflamed tissues where oxygen tension is usually low, which 
      requires the transcription factor hypoxia inducible factor (HIF)-1 for cellular 
      adaptation. To investigate whether the HIF-1 transcriptional complex plays a 
      pivotal role in the function of DCs, we compared the effects of exogenous 
      inflammatory stimuli and hypoxia on HIF-1alpha in bone marrow-derived DCs from wild 
      type and myeloid-specific HIF-1alpha knock-out mice. We showed that the Toll-like 
      receptor ligands lipopolysaccharides and cytosine-phosphatidyl-guanines 
      significantly induce HIF-1alpha mRNA and protein, leading to elevated HIF-1 target 
      gene expression of vascular endothelial growth factor. In contrast, 
      polyinosinic:polycytidylic acid did not show comparable effects. Furthermore the 
      potential to up-regulate inflammatory cytokines critically influences DC 
      function. Our data demonstrate that HIF-1alpha protein is needed for adequate 
      production of interferon-alpha and -beta. In co-cultures of DCs and cytotoxic T cells, 
      we observed that DCs lacking active HIF-1alpha protein induce significantly less 
      CD278 and granzyme B mRNA in T cells. We conclude that HIF-1alpha plays a crucial 
      role in DC interferon production and T cell activation, linking the innate and 
      adaptive immune system.
FAU - Wobben, Regina
AU  - Wobben R
AD  - Institut fur Physiologie, Universitat Duisburg-Essen, Essen, Germany.
FAU - Husecken, Yvonne
AU  - Husecken Y
FAU - Lodewick, Claudia
AU  - Lodewick C
FAU - Gibbert, Kathrin
AU  - Gibbert K
FAU - Fandrey, Joachim
AU  - Fandrey J
FAU - Winning, Sandra
AU  - Winning S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Germany
TA  - Biol Chem
JT  - Biological chemistry
JID - 9700112
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interferon Type I)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Dendritic Cells/*metabolism
MH  - Hypoxia/genetics/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Interferon Type I/biosynthesis
MH  - Interferons/*biosynthesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Real-Time Polymerase Chain Reaction
EDAT- 2013/01/31 06:00
MHDA- 2013/09/05 06:00
CRDT- 2013/01/31 06:00
PHST- 2012/11/06 00:00 [received]
PHST- 2013/01/21 00:00 [accepted]
PHST- 2013/01/31 06:00 [entrez]
PHST- 2013/01/31 06:00 [pubmed]
PHST- 2013/09/05 06:00 [medline]
AID - /j/bchm.just-accepted/hsz-2012-0320/hsz-2012-0320.xml [pii]
AID - 10.1515/hsz-2012-0320 [doi]
PST - ppublish
SO  - Biol Chem. 2013 Apr;394(4):495-505. doi: 10.1515/hsz-2012-0320.