School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea ; Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Yanbian University, Yanji 133000, China.
Oxid Med Cell Longev. 2013;2013:210563. doi: 10.1155/2013/210563. Epub 2013 Nov 14.
Endogenous carbon monoxide (CO) is produced by heme oxygenase-1 (HO)-1 which mediates the degradation of heme into CO, iron, and biliverdin. Also, CO ameliorates the human inflammatory bowel diseases and ulcerative colitis. However, the mechanism for the effect of CO on the inflammatory bowel disease has not yet been known. In this study, we showed that CO significantly increases survival percentage, body weight, colon length as well as histologic parameters in DSS-treated mice. In addition, CO inhalation significantly decreased DSS induced pro-inflammatory cytokines by inhibition of GSK-3β in mice model. To support the in vivo observation, TNF-α, iNOS and IL-10 after CO and LiCl treatment were measured in mesenteric lymph node cells (MLNs) and bone marrow-derived macrophages (BMMs) from DSS treated mice. In addition, we determined that CO potentially inhibited GSK-3β activation and decreased TNF-α and iNOS expression by inhibition of NF-κB activation in LPS-stimulated U937 and MLN cells pretreated with CO. Together, our findings indicate that CO attenuates DSS-induced colitis via inhibition of GSK-3β signaling in vitro and in vivo. Importantly, this is the first report that investigated the molecular mechanisms mediated the novel effects of CO via inhibition GSK-3β in DSS-induced colitis model.
内源性一氧化碳（CO）由血红素加氧酶-1（HO-1）产生，介导血红素降解为 CO、铁和胆绿素。此外，CO 可改善人类炎症性肠病和溃疡性结肠炎。然而，CO 对炎症性肠病影响的机制尚不清楚。在本研究中，我们发现 CO 可显著提高 DSS 处理小鼠的存活率、体重、结肠长度和组织学参数。此外，CO 吸入通过抑制 GSK-3β显著降低 DSS 诱导的促炎细胞因子。为了支持体内观察，我们在 DSS 处理小鼠的肠系膜淋巴结细胞（MLNs）和骨髓来源的巨噬细胞（BMMs）中测量了 TNF-α、iNOS 和 IL-10 后，用 CO 和 LiCl 处理。此外，我们确定 CO 通过抑制 LPS 刺激的 U937 和 MLN 细胞中 NF-κB 激活来抑制 GSK-3β激活并降低 TNF-α和 iNOS 表达。总之，我们的研究结果表明，CO 通过抑制 GSK-3β信号通路在体内外减轻 DSS 诱导的结肠炎。重要的是，这是第一项研究，通过抑制 DSS 诱导的结肠炎模型中的 GSK-3β，研究了 CO 的新型作用的分子机制。
