Plasmin inhibition protects against dextran sulfate sodium-induced colitis

溃疡性结肠炎的治疗通常在缓解症状方面有效，但不能治愈。通常情况下，这种疾病会以复发和缓解的过程发展。基质金属蛋白酶(MMPs)等酶的组织重塑被认为是炎症性肠病的一个组成部分。越来越多的证据表明，在活动期溃疡性结肠炎中，MMPs是肠粘膜中表达的主要蛋白。在此，我们研究了MMP9和纤溶酶原在DSS(葡聚糖硫酸钠)诱导的急性结肠炎动物模型中的作用。药物抑制、活性中心导向的抑制剂或PLG或MMP9的靶向基因缺失可防止DSS结肠炎期间野生型小鼠发病率的增加。这与结肠组织中炎性细胞的减少有关，并与结肠细胞因子水平升高受损有关。综上所述，我们的数据显示，PLG和MMP9的缺失强烈地抑制了急性结肠炎的炎症反应，这与缓解疾病的病程有关。

Treatment of ulcerative colitis is generally effective in relieving symptoms, but is not curative. Typically, this disease evolves with a relapsing and remitting course. Tissue remodeling by proteases like matrix metalloproteinases (MMP) have been described as a component of inflammatory bowel disease. There is mounting evidence that MMPs are the predominant proteinases expressed in the gut mucosa during active ulcerative colitis. Others and we showed that plasmin can activate several MMPs.Here, we investigated the function of MMP9 and plasminogen in a DSS (Dextran sulfate sodium) induced animal model of acute colitis. Pharmacological inhibition, an active -center-directed inhibitor or targeted gene deletion of Plg or MMP9 prevented increased morbidity of wildtype mice during DSS colitis. This was associated with a reduced inflammatory cell infiltration in colon tissues and correlated with impaired colonic cytokine level elevation. In summary, our data show that the absence of Plg and MMP9 strongly inhibits the inflammatory response in acute colitis, which is associated with alleviation of the course of the disease.