Louis E, Ribbens C, Godon A, Franchimont D, De Groote D, Hardy N, Boniver J, Belaiche J, Malaise M
Department of Gastroenterology, Inflammatory Diseases Research Group, and Department of Pathology, CHU, Liège, Belgium.
Clin Exp Immunol. 2000 May;120(2):241-6. doi: 10.1046/j.1365-2249.2000.01227.x.
Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were (i) to measure the production of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty-eight patients with IBD, including 25 with Crohn's disease and 13 with ulcerative colitis, were included. Ten controls were also studied. Biopsies were taken from inflamed and uninflamed regions and inflammation was graded both macroscopically and histologically. Organ cultures were performed for 18 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta, IL-10, MMP-3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below the sensitivity of our immunoassay in the vast majority of uninflamed samples either from controls or from those with Crohn's disease or ulcerative colitis. In inflamed mucosa, the production of these mediators increased significantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulcerative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflammatory cytokines and IL-10, as well as with the degree of macroscopic and microscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerative colitis show increased production of both MMP-3 and its tissue inhibitor, which correlates very well with production of IL-1beta, IL-6, TNF-alpha and IL-10.
炎症性肠病（IBD）的特征是持续的炎症级联反应，导致能够降解和改变肠壁结构的介质释放。我们的目的是：（i）测量IBD中炎症和非炎症结肠黏膜产生基质金属蛋白酶-3（MMP-3）及其组织抑制剂金属蛋白酶组织抑制剂-1（TIMP-1）的情况；（ii）将它们的产生与促炎细胞因子和抗炎细胞因子IL-10的产生进行关联。纳入了38例IBD患者，其中包括25例克罗恩病患者和13例溃疡性结肠炎患者。还研究了10名对照者。从炎症和非炎症区域取活检组织，并对炎症进行宏观和组织学分级。进行18小时的器官培养。使用特异性免疫测定法测量肿瘤坏死因子-α（TNF-α）、IL-6、IL-1β、IL-10、MMP-3和TIMP-1的浓度。在绝大多数来自对照者或克罗恩病或溃疡性结肠炎患者的非炎症样本中，MMP-3和TIMP-1的产生要么无法检测到，要么低于我们免疫测定法的灵敏度。在炎症黏膜中，这些介质的产生在克罗恩病（分别为P < 0.01和0.001）和溃疡性结肠炎（分别为P < 0.001和0.001）中均显著增加。在这两种情况下，介质的产生均与促炎细胞因子和IL-10的产生以及宏观和微观炎症程度显著相关。克罗恩病和溃疡性结肠炎的炎症黏膜均显示MMP-3及其组织抑制剂的产生增加，这与IL-1β、IL-6、TNF-α和IL-10的产生密切相关。
