Anti-Inflammatory Effects of Hyperbaric Oxygenation during DSS-Induced Colitis in BALB/c Mice Include Changes in Gene Expression of HIF-1α, Proinflammatory Cytokines, and Antioxidative Enzymes.
Martina MihaljInes DrenjancevicRosemary VukovicZoltán KellermayerAnita MatićMaja Tolusic LevakPéter BaloghFilip CuloMartina MihaljPublished in: Mediators of inflammation (2016)
Reactive oxygen species (ROS) and nitrogen species have an indispensable role in regulating cell signalling pathways, including transcriptional control via hypoxia inducible factor-1α (HIF-1α). 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 HIF-1α, 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 IL-1β, IL-2, and IL-6 gene expression. Gene expression and antioxidative enzyme activity were changed by the HBO2 and the inflammatory microenvironment in the gut mucosa. Strong correlation of HIF-1α mRNA level to GPx1, SOD1, and IL-6 mRNA expression suggests involvement of HIF-1α in transcriptional regulation of these genes during colonic inflammation and HBO2. This is further confirmed by a strong correlation of HIF-1α with known target genes VEGF and PGK1. 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 HIF-1α and antioxidative genes.
Keyphrases
- gene expression
- anti inflammatory
- endothelial cells
- reactive oxygen species
- oxidative stress
- genome wide
- dna methylation
- high fat diet induced
- dna damage
- cell death
- genome wide identification
- poor prognosis
- stem cells
- transcription factor
- type diabetes
- vascular endothelial growth factor
- genome wide analysis
- insulin resistance
- ulcerative colitis
- blood flow
- replacement therapy
- mesenchymal stem cells
- smoking cessation