Anti-Inflammatory Effects of Hyperbaric Oxygenation during DSS-Induced Colitis in BALB/c Mice Include Changes in Gene Expression of<i>HIF-1<i>α</i></i>, Proinflammatory Cytokines, and Antioxidative Enzymes

Abstract

Reactive oxygen species (ROS) and nitrogen species have an indispensable role in regulating cell signalling pathways, including transcriptional control via hypoxia inducible factor-1<i>α</i> (<i>HIF-1α</i>). Hyperbaric oxygenation treatment (HBO₂) increases tissue oxygen content and leads to enhanced ROS production. In the present study DSS-induced colitis has been employed in BALB/c mice as an experimental model of gut mucosa inflammation to investigate the effects of HBO₂ on <i>HIF-1α</i>, antioxidative enzyme, and proinflammatory cytokine genes during the colonic inflammation. Here we report that HBO₂ significantly reduces severity of DSS-induced colitis, as evidenced by the clinical features, histological assessment, impaired immune cell expansion and mobilization, and reversal of <i>IL-1β</i>, <i>IL-2</i>, and <i>IL-6</i> gene expression. Gene expression and antioxidative enzyme activity were changed by the HBO₂ and the inflammatory microenvironment in the gut mucosa. Strong correlation of <i>HIF-1α</i> mRNA level to <i>GPx1</i>, <i>SOD1</i>, and <i>IL-6</i> mRNA expression suggests involvement of <i>HIF-1α</i> in transcriptional regulation of these genes during colonic inflammation and HBO₂. This is further confirmed by a strong correlation of <i>HIF-1α</i> with known target genes VEGF and <i>PGK1</i>. Results demonstrate that HBO₂ has an anti-inflammatory effect in DSS-induced colitis in mice, and this effect is at least partly dependent on expression of <i>HIF-1α</i> and antioxidative genes.