Myeloid Knockout of HIF-1 α Does Not Markedly Affect HemorrhageResuscitation-Induced Inflammation and Hepatic Injury

Abstract EN

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 ( 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-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.