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首页> 外文期刊>European journal of gastroenterology and hepatology >Stromelysin-1 and macrophage metal loelastase expression in the intestinal mucosa of Crohn's disease patients treated with infliximab
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Stromelysin-1 and macrophage metal loelastase expression in the intestinal mucosa of Crohn's disease patients treated with infliximab

机译：英夫利昔单抗治疗的克罗恩病患者肠黏膜中Stromelysin-1和巨噬细胞金属纤维蛋白酶的表达

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Background and aims The mechanism by which anti-tumor necrosis factor (TNF)-alpha therapy promotes rapid closure of fistulas and mucosal wound healing in Crohn's disease (CD) remains unclear. An ex-vivo model of gut T-cell mediated injury indicated that TNF-alpha blockade prevents tissue damage concomitant with matrix metalloproteinase (WIMP) inhibition. We, therefore, hypothesized that the chimeric anti-TNF-alpha antibody infliximab facilitates wound healing in CD by downregulating tissue degrading MMPs. We focused on MMP-3 (stromelysin-1) and MMP-12 (macrophage metalloelastase) as these two enzymes have been linked to connective tissue destruction in CD.Methods Endoscopic biopsies were taken from 10 CD patients immediately before and after 10 weeks of treatment with infliximab. Before treatment, biopsies were taken from macroscopically inflamed areas, and after treatment were collected from the same locations as before treatment. The degree of mucosal damage was assessed by using a histological scoring system. MMP transcripts were detected by in-situ hybridization on paraffin sections. MMP proteins were determined by immunoblotting on mucosai homogenates.Results Six out of 10 patients had a clinical response to infliximab. MMP-3 and MMP-12 transcripts and proteins, which were highly expressed in CD inflamed mucosa, decreased after treatment in those patients who responded to infliximab. MMP-3 and MMP-12 downregulation was accompanied by a concomitant improvement of the histologic score. No change in MMP expression was found in nonresponders.Conclusion The downregulation of tissue degrading MMPs in CD mucosa may explain the wound repair capacity of infliximab in healing fistulas and ulcers.
机译：背景与目的抗肿瘤坏死因子（TNF）-α疗法促进克罗恩病（CD）瘘管快速闭合和粘膜伤口愈合的机制尚不清楚。肠道T细胞介导的损伤的体外模型表明，TNF-α阻断可防止组织损伤并伴有基质金属蛋白酶（WIMP）抑制。因此，我们假设嵌合的抗TNF-α抗体英夫利昔单抗通过下调组织降解性MMPs促进CD中的伤口愈合。我们将重点放在MMP-3（基质溶素1）和MMP-12（巨噬细胞金属弹性蛋白酶）上，因为这两种酶与CD中的结缔组织破坏有关。与英夫利昔单抗。治疗前，从肉眼可见的发炎区域进行活检，治疗后从与治疗前相同的位置收集。通过使用组织学评分系统评估粘膜损伤的程度。通过在石蜡切片上原位杂交检测MMP转录本。结果：通过对粘液藻匀浆进行免疫印迹法测定MMP蛋白。结果10例患者中有6例对英夫利昔单抗有临床反应。在对英夫利昔单抗有反应的患者中，在CD炎性粘膜中高表达的MMP-3和MMP-12转录本和蛋白质在治疗后降低。 MMP-3和MMP-12的下调伴随组织学评分的改善。结论：CD粘膜组织降解性MMPs的下调可能解释了英夫利昔单抗在瘘管和溃疡中的修复能力。

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