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-1αin liver hypoxia, injury, and inflammation after H/R with special regard to NF-κB activation was studied.Methods. Mice with a conditional HIF-1αknockout (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-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-1αKO was comparable to WT. Elevated plasma interleukin-6 (IL-6) levels after H/R were not reduced by HIF-1αKO. Local hepatic hypoxia was not significantly reduced in HIF-1αKO 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-1αin 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.
Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse
