Sato T, Nakai T, Tamura N, Okamoto S, Matsuoka K, Sakuraba A, Fukushima T, Uede T, Hibi T
Division of Gastroenterology, Department of Gastroenterology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Gut. 2005 Sep;54(9):1254-62. doi: 10.1136/gut.2004.048298.
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.
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 beta3, 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.
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 beta3 expressing macrophages infiltrated inflamed mucosa in UC and CD; in contrast, there was no expression of integrin beta3 on intestinal macrophages in normal mucosa. OPN induced production of IL-12 from LPMC in CD but not in normal controls or UC.
Increased OPN expression facilitates cytokine production and is closely involved in the Th1 immune response associated with CD.
克罗恩病（CD）是一种以Th1免疫反应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，作为一种黏附性骨基质蛋白为人所知。最近的研究表明，OPN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。本研究调查了OPN在CD中的表达及其病理生理作用。
采用酶联免疫吸附测定法测量血浆OPN浓度。使用逆转录-聚合酶链反应和蛋白质免疫印迹法测定人肠黏膜中OPN的表达，并通过免疫组织化学检查OPN的定位。通过流式细胞术评估OPN受体整合素β3在固有层单核细胞（LPMC）上的表达。通过测量细胞因子的产生来研究LPMC中OPN的功能激活。
与正常对照或溃疡性结肠炎（UC）患者相比，CD患者的血浆OPN浓度显著更高。UC和CD患者肠黏膜中的OPN上调。产生OPN的细胞为上皮细胞、产生IgG的浆细胞或部分巨噬细胞。在CD患者黏膜肉芽肿周围区域检测到OPN。表达整合素β3的巨噬细胞浸润UC和CD患者的炎症黏膜；相比之下，正常黏膜中的肠巨噬细胞上没有整合素β3的表达。OPN诱导CD患者LPMC产生IL-12，但正常对照或UC患者中则不然。
OPN表达增加促进细胞因子产生，并密切参与与CD相关的Th1免疫反应。
