Changes in inflammatory gene expression induced by hyperbaric oxygen treatment in human endothelial cells under chronic wound conditions

Hyperbaric oxygen (HBO) therapy involves the inhalation of 100% oxygen, whilst inside a chamber at greater than atmospheric pressure. It is an effective treatment for chronic diabetic wounds, although the molecular mechanisms involved remain unclear. We hypothesised that HBO could alter inflammatory gene expression in human endothelial cells via a reactive oxygen/nitrogen species-mediated pathway. Endothelial cells were exposed to a chronic wound model comprising hypoxia (2% O2 at 1 atmosphere absolute (ATA); PO2 ~ 2 kPa) in the presence of lipopolysaccharide and TNF-α for 24 h, then treated with HBO for 90 min (97.5% O2 at 2.4 ATA; PO2 ~ 237 kPa). 5 h post-HBO, 19 genes involved in adhesion, angiogenesis, inflammation and oxidative stress were downregulated. Notably, only angiogenin gene expression, which promotes both angiogenesis and nitric oxide production (reflected by increased eNOS protein expression in this study), was upregulated. This led to a decrease in endothelial IL-8 mRNA and protein, which could help alleviate inflammatory processes during chronic wound healing. This was no longer evident 22.5 h post-HBO, demonstrating the importance of daily exposures in HBO treatment protocols. These studies indicate that elevated oxygen transiently regulates inflammatory gene expression in endothelial cells, which may enhance chronic wound healing.

► We developed a chronic wound model of endothelial cells to test for gene expression.
► We tested the effect of hyperbaric oxygen on 92 pro and anti-inflammatory genes.
► Angiogenin gene expression and eNOS protein production were significantly elevated.
► The pro-inflammatory IL-8 mRNA and protein levels decreased post-treatment.
► Hyperoxia regulates specific inflammatory gene expression in endothelial cells.