Increased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease
Increased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease
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DOI：
10.1046/j.1365-2249.2000.01227.x
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发表时间：
2000-05-01
影响因子：
4.6
通讯作者：
Malaise, M
中科院分区：
文献类型：
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作者：
Louis, E;Ribbens, C;Malaise, M
炎症性肠病（IBD）的特征在于持续的炎症级联反应，其引起能够降解和改变肠壁结构的介质的释放。我们的目的是（i）测量IBD中炎症和非炎症结肠粘膜的基质金属蛋白酶-3（MMP-3）及其组织抑制剂金属蛋白酶组织抑制剂-1（TIMP-1）的产生，以及（ii）将它们的产生与促炎细胞因子和抗炎细胞因子IL-10的产生相关联。纳入38例IBD患者，包括25例克罗恩病和13例溃疡性结肠炎。还研究了10个对照组。从发炎和未发炎区域取活检，并对炎症进行肉眼和组织学分级。进行器官培养18 h。使用特异性免疫测定法测量肿瘤坏死因子-α（TNF-α）、IL-6、IL-1 β、IL-10、MMP-3和TIMP-1浓度。MMP-3和TIMP-1的产生在来自对照或来自克罗恩病或溃疡性结肠炎的绝大多数未发炎样品中不可检测或低于我们的免疫测定的灵敏度。在炎症粘膜中，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）中显著增加。两种情况下的介体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着相关。克罗恩病和溃疡性结肠炎的发炎粘膜均显示MMP-3及其组织抑制剂的产生增加，这与IL-1 β、IL-6、TNF-α和IL-10的产生非常相关。
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-1 beta, 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-1 beta, IL-6, TNF-alpha and IL-10.