title: Changes in inflammatory gene expression induced by hyperbaric oxygen treatment in human endothelial cells under chronic wound conditions.
abstract: 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% O(2) at 1 atmosphere absolute (ATA); PO(2) ~2 kPa) in the presence of lipopolysaccharide and TNF-α for 24h, then treated with HBO for 90 min (97.5% O(2) at 2.4 ATA; PO(2) ~237 kPa). 5h 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 22.5h 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.
authors: Peninsula Medical School, University of Exeter, Exeter, Devon, EX1 2LU, UK.
authors: Alexandra C
authors: AC
authors: Kendall
authors: Jacqueline L
authors: JL
authors: Whatmore
authors: Lorna W
authors: LW
authors: Harries
authors: Paul G
authors: PG
authors: Winyard
authors: Gary R
authors: GR
authors: Smerdon
authors: Paul
authors: P
authors: Eggleton
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D002908:Chronic Disease; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006931:Hyperbaric Oxygenation; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics / Q000502:physiology; D014947:Wounds and Injuries / Q000235:genetics* / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III