Increased Enterocyte Apoptosis in Inflamed Areas of Crohn’s Disease
Increased Enterocyte Apoptosis in Inflamed Areas of Crohn’s Disease
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DOI：
10.1097/01.dcr.0000089118.20964.12
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发表时间：
2003-11
影响因子：
3.9
通讯作者：
A. Di Sabatino;R. Ciccocioppo;O. Luinetti;L. Ricevuti;R. Morera;M. Cifone;E. Solcia;G. Corazza
中科院分区：
文献类型：
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作者：
A. Di Sabatino;R. Ciccocioppo;O. Luinetti;L. Ricevuti;R. Morera;M. Cifone;E. Solcia;G. Corazza
摘要目的：由于肠上皮细胞凋亡的增加已与一些慢性炎症性疾病的发病机制，我们的研究的目的是调查上皮细胞死亡克罗恩病和可能的作用，Fas-Fas配体系统，E-钙粘蛋白，基质金属蛋白酶-1在这种情况下调节肠上皮细胞凋亡。方法：从20例克罗恩病患者和20例经证实患有功能性腹泻的受试者的肉眼可见受累和未受累区域收集内镜回肠和结肠活检标本。根据临床和病理标准确定诊断。活检标本进行传统的组织学和免疫组化评估Fas，Fas配体，E-钙粘蛋白，Ki 67抗原，和基质金属蛋白酶-1的表达。对于凋亡细胞的原位检测，使用末端脱氧核苷酸转移酶介导的地高辛-脱氧尿苷三磷酸缺口末端标记。结果：克罗恩病患者病变区肠上皮细胞凋亡率高于正常肠上皮细胞。克罗恩病未受累肠段与正常肠段比较，差异无统计学意义。在克罗恩病中，肠上皮细胞Fas和固有层单核细胞Fas配体表达与对照组无差异。E-钙粘蛋白强烈表达的上皮细胞在正常和发炎的肠，除了再生上皮细胞的基础上的溃疡，在减少E-钙粘蛋白的表达进行了观察。与对照组相比，克罗恩病患者受累或未受累区域的Ki 67阳性增殖上皮细胞数量没有差异。基质金属蛋白酶-1的过度表达被发现在参与与未参与克罗恩病地区和正常组织相比，基质金属蛋白酶-1的表达和肠上皮细胞凋亡之间的显着正相关性被发现在克罗恩病炎症地区。结论：肠细胞凋亡在克罗恩病累及区域增加。这种增加不是由Fas-Fas配体机制或异常的E-钙粘蛋白分布介导的。固有层单核细胞释放基质金属蛋白酶-1可能是克罗恩病肠上皮细胞凋亡增加的机制之一。
AbstractPURPOSE: Because increased enterocyte apoptosis has been associated with the pathogenesis of several chronic inflammatory diseases, the aim of our study was to investigate epithelial cell death in Crohn’s disease and the possible role of the Fas-Fas ligand system, E-cadherin, and matrix metalloproteinase-1 in modulating enterocyte apoptosis in this condition. METHODS: Endoscopic ileal and colonic biopsy specimens were collected from macroscopically involved and uninvolved areas of 20 patients with Crohn’s disease and 20 subjects who proved to have functional diarrhea. Diagnosis was established by clinical and pathologic criteria. Biopsy specimens were processed for traditional histology and for the immunohistochemical evaluation of Fas, Fas ligand, E-cadherin, Ki67 antigen, and matrix metalloproteinase-1 expression. For the in situ detection of apoptotic cells, terminal deoxynucleotidyl transferase–mediated digoxigenin-deoxyuridine triphosphate nick end labeling was used. RESULTS: The percentages of apoptotic enterocytes were higher in involved than in uninvolved areas of Crohn’s disease patients and normal intestine. No significant difference was found between Crohn’s disease uninvolved areas and normal intestine. In Crohn’s disease, both enterocyte Fas and lamina propria mononuclear cell Fas ligand expression did not differ from controls. E-cadherin was strongly expressed by epithelium in both normal and inflamed intestine, except for the regenerative epithelium over the base of the ulcers, where a reduced E-cadherin expression was observed. The number of Ki67-positive proliferating epithelial cells did not differ either in involved or uninvolved areas of Crohn’s disease patients compared with controls. A lamina propria overexpression of matrix metalloproteinase-1 was found in involved compared with uninvolved Crohn’s disease areas and normal tissue, and a significant positive correlation between matrix metalloproteinase-1 expression and enterocyte apoptosis was found in Crohn’s disease inflamed areas. CONCLUSIONS: Enterocyte apoptosis is increased in involved areas of Crohn’s disease. This increase is not mediated by a Fas-Fas ligand mechanism or by an abnormal E-cadherin distribution. Increased matrix metalloproteinase-1 release from lamina propria mononuclear cells might be one of the possible mechanisms responsible for the increased enterocyte apoptosis in Crohn’s disease.