Myeloid knockout of HIF-1α does not markedly affect hemorrhage/resuscitation-induced inflammation and hepatic injury

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
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.
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Author:Gerald Wetzel, Borna Relja, Alexander Klarner, Dirk Henrich, Nathalie Dehne, Bernhard Brühne, Mark Lehnert, Ingo Marzi
URN:urn:nbn:de:hebis:30:3-373608
DOI:http://dx.doi.org/10.1155/2014/930419
ISSN:1466-1861
ISSN:0962-9351
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24991092
Parent Title (English):Mediators of inflammation
Publisher:Hindawi Publishing Corp.
Place of publication:Sylvania, Ohio
Document Type:Article
Language:English
Date of Publication (online):2014/06/01
Date of first Publication:2014/06/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2015/04/25
Volume:2014
Issue:Article ID 930419
Pagenumber:11
Note:
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.
HeBIS PPN:369126629
Institutes:Medizin
Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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