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趋化因子MCP-1和RANTES编码基因在人类炎症性肠病中的差异原位表达

Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease.

作者信息

Mazzucchelli L, Hauser C, Zgraggen K, Wagner H E, Hess M W, Laissue J A, Mueller C

机构信息

Institute of Pathology, University of Bern, Switzerland.

出版信息

J Pathol. 1996 Feb;178(2):201-6. doi: 10.1002/(SICI)1096-9896(199602)178:2<201::AID-PATH440>3.0.CO;2-4.

DOI:10.1002/(SICI)1096-9896(199602)178:2<201::AID-PATH440>3.0.CO;2-4
PMID:8683390
Abstract

Two chemotactic cytokines, monocyte chemoattractant protein-1 (MCP-1) and RANTES, possibly contribute to the recruitment and activation of leukocytes in inflamed tissues. The expression of these cytokine genes was evaluated in tissue sections from resected bowel segments of 14 patients with inflammatory bowel disease (IBD) and seven control patients by use of 35S-labelled antisense RNA probes. MCP-1 and RANTES transcripts were generally increased in the intestinal mucosa of patients with IBD, compared with controls. Whereas MCP-1 gene expression in the mucosa was restricted to the lamina propria, the gene coding for RANTES was expressed in intraepithelial lymphocytes and in the subepithelial lamina propria. Furthermore, MCP-1 mRNA, but not RANTES mRNA, was abundant in vessel-associated cells, such as endothelial cells, medial smooth muscle cells, and intraluminal cells; in smooth muscle cells of the intestinal tunica muscularis; and in cells of the myenteric plexus. Compared with controls, a significant increase of MCP-1-expressing cells was observed in tissue specimens from patients with IBD, in endothelial cells of venules, and in cells present in the lumen of intestinal vessels. Conversely, the expression of MCP-1 mRNA in smooth muscle cells and myenteric plexus cells appeared to be comparable in control and diseased intestines. The increased number of MCP-1 and RANTES mRNA-expressing cells in mucosa from patients with IBD suggests that these cytokines play a role in the pathogenesis of mucosal inflammation. Furthermore, the expression of the MCP-1 gene in vessel-associated cells may indicate its involvement in mechanisms regulating the adhesion of blood monocytes to endothelial cells.

摘要

两种趋化性细胞因子,单核细胞趋化蛋白-1(MCP-1)和调节激活正常T细胞表达和分泌的因子(RANTES),可能在炎症组织中白细胞的募集和激活过程中发挥作用。通过使用35S标记的反义RNA探针,在14例炎症性肠病(IBD)患者和7例对照患者切除肠段的组织切片中评估了这些细胞因子基因的表达。与对照组相比,IBD患者肠黏膜中MCP-1和RANTES转录本普遍增加。虽然黏膜中MCP-1基因表达仅限于固有层,但编码RANTES的基因在上皮内淋巴细胞和上皮下固有层中表达。此外,MCP-1 mRNA在血管相关细胞中丰富,如内皮细胞、中层平滑肌细胞和管腔内细胞;在肠肌层的平滑肌细胞中;以及在肌间神经丛的细胞中,但RANTES mRNA并非如此。与对照组相比,在IBD患者的组织标本、小静脉内皮细胞和肠血管腔内的细胞中观察到表达MCP-1的细胞显著增加。相反,在对照肠和患病肠中,平滑肌细胞和肌间神经丛细胞中MCP-1 mRNA的表达似乎相当。IBD患者黏膜中表达MCP-1和RANTES mRNA的细胞数量增加表明这些细胞因子在黏膜炎症的发病机制中起作用。此外,MCP-1基因在血管相关细胞中的表达可能表明其参与调节血液单核细胞与内皮细胞黏附的机制。

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