title: Myeloid knockout of HIF-1 α does not markedly affect hemorrhage/resuscitation-induced inflammation and hepatic injury.
abstract: BACKGROUND
  Hypoxia-inducible factor-1 α (HIF-1 α ) and NF- κ B play important roles in the inflammatory response after hemorrhagic shock and resuscitation (H/R). Here, the role of myeloid HIF-1 α in liver hypoxia, injury, and inflammation after H/R with special regard to NF- κ B activation was studied.
  
  
  METHODS
  Mice with a conditional HIF-1 α knockout (KO) in myeloid cell-line and wild-type (WT) controls were hemorrhaged for 90 min (30 ± 2 mm Hg) and resuscitated. Controls underwent only surgical procedures.
  
  
  RESULTS
  After six hours, H/R enhanced the expression of HIF-1 α -induced genes vascular endothelial growth factor (VEGF) and adrenomedullin (ADM). In KO mice, this was not observed. H/R-induced liver injury in HIF-1 α KO was comparable to WT. Elevated plasma interleukin-6 (IL-6) levels after H/R were not reduced by HIF-1 α KO. Local hepatic hypoxia was not significantly reduced in HIF-1 α 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-1 α 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-1 α, are rather key modulators of inflammation after H/R in our model.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wetzel
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Relja
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Klarner
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Henrich
authors.affiliation: Institute of Biochemistry I/ZAFES, Goethe University, 60590 Frankfurt, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Dehne
authors.affiliation: Institute of Biochemistry I/ZAFES, Goethe University, 60590 Frankfurt, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Brühne
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lehnert
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Marzi
mesh_terms: D000818:Animals; D005260:Female; D006470:Hemorrhage / Q000235:genetics / Q000378:metabolism*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency* / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D008107:Liver Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit