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单核细胞趋化蛋白1基因在肠上皮细胞及炎症性肠病黏膜中的表达

Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa.

作者信息

Reinecker H C, Loh E Y, Ringler D J, Mehta A, Rombeau J L, MacDermott R P

机构信息

Division of Gastroenterology, University of Pennsylvania Medical Center, Philadelphia.

出版信息

Gastroenterology. 1995 Jan;108(1):40-50. doi: 10.1016/0016-5085(95)90006-3.

DOI:10.1016/0016-5085(95)90006-3
PMID:7806062
Abstract

BACKGROUND

Monocyte-chemoattractant protein 1 (MCP-1) activates macrophages and increases the migration of monocytes into tissue during inflammation. It was hypothesized that MCP-1 expression is involved in intestinal inflammation.

METHODS

MCP-1 protein was detected by immunohistochemistry and immunoprecipitation. Biological activity of MCP-1 was assessed using a chemotactic assay. MCP-1 messenger RNA (mRNA) levels were measured by quantitative reverse-transcription polymerase chain reaction.

RESULTS

In normal mucosa, MCP-1 was predominantly present in surface epithelium. In contrast, inflamed mucosa from patients with ulcerative colitis or Crohn's disease contained multiple cells immunoreactive for MCP-1, including spindle cells, mononuclear cells, and endothelial cells. Furthermore, MCP-1 mRNA expression was markedly increased in inflamed intestinal biopsy specimens from patients with inflammatory bowel disease. MCP-1 was detected in isolated intestinal epithelial cells and in conditioned media from Caco-2 cells. Caco-2 cell-conditioned media stimulated monocyte chemotaxis activity that was inhibited by anti-MCP-1 antibodies. Constituitive MCP-1 mRNA levels in Caco-2 cells were up-regulated by interleukin 1 beta and down-regulated by dexamethasone.

CONCLUSIONS

In addition to lamina propria macrophages, endothelial cells, and spindle cells, intestinal epithelial cells are able to produce MCP-1. MCP-1 is expressed constitutively in the intestinal colonic mucosa and is up-regulated during inflammation.

摘要

背景

单核细胞趋化蛋白1(MCP - 1)可激活巨噬细胞,并在炎症过程中增加单核细胞向组织内的迁移。据推测,MCP - 1的表达与肠道炎症有关。

方法

采用免疫组织化学和免疫沉淀法检测MCP - 1蛋白。使用趋化试验评估MCP - 1的生物活性。通过定量逆转录聚合酶链反应测量MCP - 1信使核糖核酸(mRNA)水平。

结果

在正常黏膜中,MCP - 1主要存在于表面上皮细胞。相比之下,溃疡性结肠炎或克罗恩病患者的炎症黏膜含有多种对MCP - 1呈免疫反应性的细胞,包括梭形细胞、单核细胞和内皮细胞。此外,炎症性肠病患者的炎症肠道活检标本中MCP - 1 mRNA表达明显增加。在分离的肠上皮细胞和Caco - 2细胞的条件培养基中检测到MCP - 1。Caco - 2细胞条件培养基刺激单核细胞趋化活性,该活性被抗MCP - 1抗体抑制。Caco - 2细胞中组成性MCP - 1 mRNA水平被白细胞介素1β上调,并被地塞米松下调。

结论

除固有层巨噬细胞、内皮细胞和梭形细胞外,肠上皮细胞也能够产生MCP - 1。MCP - 1在结肠黏膜中组成性表达,并在炎症期间上调。

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