TY  - JOUR
A1  - Wetzel, Gerald
A1  - Relja, Borna
A1  - Klarner, Alexander
A1  - Henrich, Dirk
A1  - Dehne, Nathalie
A1  - Brühne, Bernhard
A1  - Lehnert, Mark
A1  - Marzi, Ingo
T1  - Myeloid knockout of HIF-1α does not markedly affect hemorrhage/resuscitation-induced inflammation and hepatic injury
T2  - Mediators of inflammation
N2  - Background: Hypoxia-inducible factor-1α (HIF-1α) and NF-κB play important roles in the inflammatory response after hemorrhagic shock and resuscitation (H/R). Here, the role of myeloid HIF-1α in liver hypoxia, injury, and inflammation after H/R with special regard to NF-κB activation was studied.
Methods: Mice with a conditional HIF-1α knockout (KO) in myeloid cell-line and wild-type (WT) controls were hemorrhaged for 90 min ( mm Hg) and resuscitated. Controls underwent only surgical procedures.
Results: After six hours, H/R enhanced the expression of HIF-1α-induced genes vascular endothelial growth factor (VEGF) and adrenomedullin (ADM). In KO mice, this was not observed. H/R-induced liver injury in HIF-1α KO was comparable to WT. Elevated plasma interleukin-6 (IL-6) levels after H/R were not reduced by HIF-1α KO. Local hepatic hypoxia was not significantly reduced in HIF-1α KO compared to controls after H/R. H/R-induced NF-κB phosphorylation in liver did not significantly differ between WT and KO.
Conclusions: Here, deleting HIF-1α in myeloid cells and thereby in Kupffer cells was not protective after H/R. This data indicates that other factors, such as NF-κB, due to its upregulated phosphorylation in WT and KO mice, contrary to HIF-1α, are rather key modulators of inflammation after H/R in our model.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37360
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-373608
SN  - 1466-1861
SN  - 0962-9351
N1  - Copyright © 2014 G. Wetzel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 2014
IS  - Article ID 930419
PB  - Hindawi Publishing Corp.
CY  - Sylvania, Ohio
ER  -