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
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
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DOI：
10.1155/2016/7141430
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发表时间：
2016-01-01
影响因子：
4.6
通讯作者：
Mihalj, Martina
中科院分区：
文献类型：
--
作者：
Novak, Sanja;Drenjancevic, Ines;Mihalj, Martina
活性氧 (ROS) 和氮在调节细胞信号通路中发挥着不可或缺的作用，包括通过缺氧诱导因子 1 α (HIF-1 α) 进行转录控制。高压氧治疗 (HBO2) 会增加组织氧含量并导致 ROS 产生增加。在本研究中，DSS诱导的结肠炎已在BALB/c小鼠中用作肠粘膜炎症的实验模型，以研究HBO2在结肠炎症期间对HIF-1α、抗氧化酶和促炎细胞因子基因的影响。在此，我们报告说，HBO2 显着降低了 DSS 诱导的结肠炎的严重程度，临床特征、组织学评估、免疫细胞扩增和动员受损以及 IL-1β、IL-2 和 IL-6 基因表达的逆转证明了这一点。 HBO2 和肠粘膜炎症微环境改变了基因表达和抗氧化酶活性。 HIF-1 α mRNA 水平与 GPx1、SOD1 和 IL-6 mRNA 表达强相关，表明 HIF-1 α 参与结肠炎症和 HBO2 期间这些基因的转录调节。 HIF-1 α 与已知靶基因 VEGF 和 PGK1 的强相关性进一步证实了这一点。结果表明，HBO2 对 DSS 诱导的小鼠结肠炎具有抗炎作用，并且这种作用至少部分依赖于 HIF-1 α 和抗氧化基因的表达。
Reactive oxygen species (ROS) and nitrogen species have an indispensable role in regulating cell signalling pathways, including transcriptional control via hypoxia inducible factor-1 alpha (HIF-1 alpha). 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-1 alpha, 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-1 beta, 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-1 alpha mRNA level to GPx1, SOD1, and IL-6 mRNA expression suggests involvement of HIF-1 alpha in transcriptional regulation of these genes during colonic inflammation and HBO2. This is further confirmed by a strong correlation of HIF-1 alpha 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-1 alpha and antioxidative genes.