Food-Grade Bacteria Expressing Elafin Protect Against Inflammation and Restore Colon Homeostasis
Food-Grade Bacteria Expressing Elafin Protect Against Inflammation and Restore Colon Homeostasis
复制标题
DOI：
10.1126/scitranslmed.3004212
复制
发表时间：
2012-10-31
影响因子：
17.1
通讯作者：
Vergnolle, Nathalie
中科院分区：
文献类型：
--
作者：
Motta, Jean-Paul;Bermudez-Humaran, Luis G.;Vergnolle, Nathalie
Elafin是一种在健康肠粘膜中表达的天然蛋白水解酶抑制剂，在体外和动物模型中具有多效性抗炎特性。我们发现在炎症性肠病(IBD)患者的黏膜中Elafin的表达减少。这一缺陷与结肠组织中的弹性分解活性(弹性酶样蛋白分解)增加有关。我们设计了两株食品级乳酸菌(LAB)来表达Elafin，并将Elafin输送到结肠的炎症部位，以评估表达Elafin的LAB的潜在治疗益处。在急性和慢性结肠炎模型中，口服表达弹性蛋白的LAB可降低弹性溶解活性和炎症反应，并恢复肠道内环境平衡。此外，当培养的人肠上皮细胞被LAB分泌的Elafin处理时，炎症的上皮细胞受到保护，使其免受肠道通透性增加以及细胞因子和趋化因子的释放，这两者都是IBD相关的肠道功能障碍的特征。综上所述，这些结果表明口服实验室分泌的Elafin可能对治疗人类IBD有用。
Elafin, a natural protease inhibitor expressed in healthy intestinal mucosa, has pleiotropic anti-inflammatory properties in vitro and in animal models. We found that mucosal expression of Elafin is diminished in patients with inflammatory bowel disease (IBD). This defect is associated with increased elastolytic activity (elastase-like proteolysis) in colon tissue. We engineered two food-grade strains of lactic acid bacteria (LAB) to express and deliver Elafin to the site of inflammation in the colon to assess the potential therapeutic benefits of the Elafin-expressing LAB. In mousemodels of acute and chronic colitis, oral administration of Elafin-expressing LAB decreased elastolytic activity and inflammation and restored intestinal homeostasis. Furthermore, when cultures of human intestinal epithelial cells were treated with LAB secreting Elafin, the inflamed epithelium was protected from increased intestinal permeability and from the release of cytokines and chemokines, both of which are characteristic of intestinal dysfunction associated with IBD. Together, these results suggest that oral delivery of LAB secreting Elafin may be useful for treating IBD in humans.