Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis
Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis
复制标题
DOI：
10.1152/ajpgi.00132.2007
复制
发表时间：
2007-10-01
影响因子：
4.5
通讯作者：
Threadgill, Deborah S.
中科院分区：
文献类型：
--
作者：
Carroll, Ian M.;Andrus, Jason M.;Threadgill, Deborah S.
使用白细胞介素 10 缺陷小鼠结肠炎模型表达锰超氧化物歧化酶的加氏乳杆菌的抗炎特性。 Am J Physiol Gastrointest Liver Physiol 293：G729-G738，2007。首次发表于 2007 年 7 月 19 日； doi:10.1152/ajpgi.00132.2007.-新出现的证据表明活性氧 (ROS) 与炎症性肠病 (IBD) 的发病机制有关。尽管肠上皮细胞产生 ROS 中和酶超氧化物歧化酶 (SOD)，但 IBD 患者发炎组织中铜/锌 (Cu/Zn) 和锰 (Mn) SOD 的蛋白质和活性水平受到干扰。因此，我们使用加氏乳杆菌作为递送载体，研究了来自嗜热链球菌的 MnSOD 减轻白细胞介素 (IL) 10 缺陷小鼠结肠炎症状的能力。 13-15 只 IL-10 缺陷小鼠组不进行治疗或补充天然 L.gasseri 或表达 MnSOD 的 L.gasseri 4 周。收集结肠组织并对炎症进行组织学评分。通过免疫组织化学研究先天免疫细胞的存在，并通过定量 PCR 测定宿主抗氧化反应。结果表明，L.gasseri 在小鼠体内可稳定维持至少 3 天。与未治疗的对照组相比，产生 MnSOD 的 L.gasseri 显着减少了 IL-10 缺陷小鼠的炎症（P < 0.05），而天然 L.gasseri 和产生 MnSOD 的抗炎作用在雄性中更为明显。加氏乳杆菌的抗炎作用与中性粒细胞和巨噬细胞浸润的减少有关。从对照小鼠和益生菌处理的 IL-10 缺陷小鼠获得的结肠组织中，抗氧化基因的转录是相同的。这项研究表明，L.gasseri 产生的 MnSOD 具有显着的抗炎活性，可降低 IL-10 缺陷小鼠结肠炎的严重程度。
Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. Am J Physiol Gastrointest Liver Physiol 293: G729-G738, 2007. First published July 19, 2007; doi:10.1152/ajpgi.00132.2007.-Emerging evidence has implicated reactive oxygen species (ROS) in the pathogenesis of inflammatory bowel disease (IBD). Although intestinal epithelial cells produce the ROS-neutralizing enzyme superoxide dismutase (SOD), the protein and activity levels of copper/zinc (Cu/Zn) and manganese (Mn) SOD are perturbed in inflamed tissues of IBD patients. Thus we investigated the ability of MnSOD from Streptococcus thermophilus to reduce colitis symptoms in interleukin (IL) 10-deficient mice using Lactobacillus gasseri as a delivery vehicle. Cohorts of 13-15 IL-10-deficient mice were left untreated or supplemented with native L. gasseri or L. gasseri expressing MnSOD for 4 wk. Colonic tissue was collected and inflammation was histologically scored. The presence of innate immune cells was investigated by immunohistochemistry and the host antioxidant response was determined by quantitative PCR. It was demonstrated that L. gasseri was stably maintained in mice for at least 3 days. L. gasseri producing MnSOD significantly reduced inflammation in IL-10-deficient mice compared with untreated controls (P < 0.05), whereas the anti-inflammatory effects of both native and MnSOD producing L. gasseri were more pronounced in males. The anti-inflammatory effects of L. gasseri were associated with a reduction in the infiltration of neutrophils and macrophages. Transcripts of antioxidant genes were equivalent in colonic tissues obtained from control and probiotic-treated IL-10-deficient mice. This study demonstrates that L. gasseri producing MnSOD has significant anti-inflammatory activity that reduces the severity of colitis in the IL-10-deficient mouse.