Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response
Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response
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DOI：
10.1136/gut.2004.048298
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发表时间：
2005-09-01
期刊：
影响因子：
24.5
通讯作者：
Hibi, T
中科院分区：
文献类型：
--
作者：
Sato, T;Nakai, T;Hibi, T
背景和目标：克罗恩病（CD）是一种以Th 1免疫应答为特征的慢性炎症性肠病，其发病机制尚不清楚。骨桥蛋白（OPN）是一种磷蛋白，被称为粘附性骨基质蛋白。最近的研究表明，骨桥蛋白在淋巴细胞迁移、肉芽肿形成和白细胞介素12（IL-12）产生中起重要作用。本研究探讨了骨桥蛋白在CD中的表达及其病理生理作用。方法：采用酶联免疫吸附法测定血浆骨桥蛋白浓度。采用逆转录-聚合酶链反应和蛋白质印迹法检测人肠粘膜中OPN的表达，并采用免疫组化法检测OPN的定位。通过流式细胞术评估固有层单核细胞（LPMC）上整合素β（3）（一种OPN受体）的表达。OPN在LPMC中的功能活化通过测量细胞因子的产生来研究。结果：CD患者的血浆OPN浓度显著高于正常对照组或溃疡性结肠炎（UC）患者。UC和CD患者肠粘膜中OPN表达上调。OPN产生细胞是上皮细胞或IgG产生浆细胞，或部分巨噬细胞。在CD的粘膜肉芽肿周围区域检测到OPN。在UC和CD中，表达整合素b3的巨噬细胞浸润炎症粘膜;相反，在正常粘膜中，肠巨噬细胞上没有整合素b3的表达。OPN诱导CD中LPMC产生IL-12，但在正常对照组或UC中没有。结论：OPN表达增加有利于细胞因子的产生，并密切参与CD相关的Th 1免疫应答。
Background and aims: The pathogenesis of Crohn's disease ( CD), a chronic inflammatory bowel disease characterised by a Th1 immune response, remains unclear. Osteopontin (OPN) is a phosphoprotein known as an adhesive bone matrix protein. Recent studies have shown that OPN plays an important role in lymphocyte migration, granuloma formation, and interleukin 12 (IL-12) production. The present study investigated expression and the pathophysiological role of OPN in CD.Methods: Plasma OPN concentration was measured by enzyme linked immunosorbent assay. Expression of OPN in human intestinal mucosa was determined using reverse transcription-polymerase chain reaction and western blot, and localisation of OPN was examined by immunohistochemistry. Expression of integrin beta(3), an OPN receptor, on lamina propria mononuclear cells (LPMC) was assessed by flow cytometry. Functional activation of OPN in LPMC was investigated by measuring the production of cytokines.Results: Plasma OPN concentration was significantly higher in patients with CD compared with normal controls or patients with ulcerative colitis (UC). OPN was upregulated in intestinal mucosa from UC and CD patients. OPN producing cells were epithelial or IgG producing plasma cells, or partial macrophages. OPN was detected in areas surrounding granuloma from mucosa in CD. Integrin b3 expressing macrophages infiltrated inflamed mucosa in UC and CD; in contrast, there was no expression of integrin b3 on intestinal macrophages in normal mucosa. OPN induced production of IL-12 from LPMC in CD but not in normal controls or UC.Conclusions: Increased OPN expression facilitates cytokine production and is closely involved in the Th1 immune response associated with CD.