Lippert E, Gunckel M, Brenmoehl J, Bataille F, Falk W, Scholmerich J, Obermeier F, Rogler G
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
Clin Exp Immunol. 2008 May;152(2):285-97. doi: 10.1111/j.1365-2249.2008.03618.x. Epub 2008 Mar 10.
Recently we identified galectin-3 (gal-3), which is secreted by colonic epithelial cells (CEC), to be a strong activator of colonic lamina propria fibroblasts (CLPF). Modulation of CLPF function may play a role during stricture and fistula formation in inflammatory bowel disease (IBD). Therefore, we investigated further the expression of gal-3 and effects on CLPF. The aim of this study is to perform a direct comparison of gal-3 between tissue from healthy controls and from patients with either Crohn's disease (CD) or ulcerative colitis (UC). CEC, CLPF and intestinal macrophages (IMAC) were isolated from control and IBD colonic tissue. Interleukin-8 secretion as a readout of CLPF activation was quantified by enzyme-linked immunosorbent assay. Gal-3 in cell cultures and tissue samples was evaluated by Western blot, immunofluorescence and immunohistochemistry. CLPF-migration was assayed in the 48-well modified Boyden chamber. Gal-3 expression was found in all segments of the colon. In the terminal ileum, less gal-3 was found compared with the colon. Immunohistochemistry and immunofluorescence revealed a homogenous distribution of gal-3 in CEC and IMAC of control mucosa and UC. However, significantly less gal-3 was found in IMAC from CD patients. In CD fistulae and stenoses, gal-3 expression was reduced significantly and barely detectable. In co-incubation studies lactose reduced significantly the CLPF-stimulatory potential of gal-3, indicating that the C-terminal domain of gal-3 is responsible for CLPF activation. Gal-3 stimulated CLPF migration in CLPF derived from fistulae. In conclusion, gal-3 expression is down-regulated in CD-fistulae and stenoses as well as in IMAC in CD patients. Gal-3 induces migration of CLPF derived from fistulae. Its role for stricture and fistula formation warrants further investigation.
最近，我们发现由结肠上皮细胞（CEC）分泌的半乳糖凝集素-3（gal-3）是结肠固有层成纤维细胞（CLPF）的强效激活剂。CLPF功能的调节可能在炎症性肠病（IBD）的狭窄和瘘管形成过程中起作用。因此，我们进一步研究了gal-3的表达及其对CLPF的影响。本研究的目的是直接比较健康对照者与克罗恩病（CD）或溃疡性结肠炎（UC）患者组织中的gal-3。从对照和IBD结肠组织中分离出CEC、CLPF和肠道巨噬细胞（IMAC）。通过酶联免疫吸附测定法定量白细胞介素-8分泌，作为CLPF激活的读数。通过蛋白质免疫印迹、免疫荧光和免疫组织化学评估细胞培养物和组织样本中的gal-3。在48孔改良博伊登小室中测定CLPF迁移。在结肠的所有节段均发现有gal-3表达。在回肠末端，与结肠相比gal-3含量较少。免疫组织化学和免疫荧光显示，gal-3在对照黏膜和UC的CEC和IMAC中呈均匀分布。然而，在CD患者的IMAC中发现gal-3明显较少。在CD瘘管和狭窄部位，gal-3表达显著降低且几乎检测不到。在共孵育研究中，乳糖显著降低了gal-3对CLPF的刺激潜能，表明gal-3的C末端结构域负责CLPF的激活。gal-3刺激来自瘘管的CLPF迁移。总之，gal-3在CD瘘管和狭窄部位以及CD患者的IMAC中表达下调。gal-3诱导来自瘘管的CLPF迁移。其在狭窄和瘘管形成中的作用值得进一步研究。
