Müller Stefan, Schaffer Thomas, Flogerzi Beatrice, Fleetwood Andrew, Weimann Rosemarie, Schoepfer Alain M, Seibold Frank
Department of Clinical Research, Division of Gastroenterology, University Hospital, University of Bern, Switzerland.
Inflamm Bowel Dis. 2006 Jul;12(7):588-97. doi: 10.1097/01.MIB.0000225341.37226.7c.
Galectins are involved at different stages in inflammation. Galectin-3, although mostly described as proinflammatory, can also act as an immunomodulator by inducing apoptosis in T cells. The present study aims to determine galectin-3 expression in the normal and inflamed intestinal mucosa and to define its role in T cell activity.
Galectin-3 was detected by quantitative polymerase chain reaction with total RNA from endoscopic biopsies and by immunohistochemistry. Biopsies and peripheral blood mononuclear cells (PBMC) were stimulated in vitro and were used to assess the functional consequences of inhibition or exogenous addition of galectin-3.
Galectin-3 is expressed at comparable levels in controls and inflammatory bowel disease (IBD) patients in remission. In the normal mucosa, galectin-3 protein was mainly observed in differentiated enterocytes, preferentially at the basolateral side. However, galectin-3 was significantly downregulated in inflamed biopsies from IBD patients. Ex vivo stimulation of uninflamed biopsies with tumor necrosis factor led to similar galectin-3 messenger RNA downregulation as in vivo. When peripheral blood mononuclear cells (PBMC) were analyzed, galectin-3 was mainly produced by monocytes. Upon mitogen stimulation, we observed increased proliferation and decreased activation-induced cell death of peripheral blood T cells in the presence of galectin-3-specific small interfering RNA. In contrast, exogenous addition of recombinant galectin-3 led to reduced proliferation of mitogen-stimulated peripheral blood T cells.
Our results suggest that downregulation of epithelial galectin-3 in the inflamed mucosa reflects a normal immunological consequence, whereas under noninflammatory conditions, its constitutive expression may help to prevent inappropriate immune responses against commensal bacteria or food compounds. Therefore, galectin-3 may prove valuable for manipulating disease activity.
半乳糖凝集素参与炎症反应的不同阶段。半乳糖凝集素-3虽然大多被描述为促炎因子，但也可通过诱导T细胞凋亡发挥免疫调节作用。本研究旨在确定正常和炎症性肠黏膜中半乳糖凝集素-3的表达情况，并明确其在T细胞活性中的作用。
采用定量聚合酶链反应从内镜活检获得的总RNA中检测半乳糖凝集素-3，并进行免疫组织化学检测。活检组织和外周血单个核细胞（PBMC）在体外进行刺激，用于评估抑制或外源性添加半乳糖凝集素-3的功能后果。
对照组和缓解期炎症性肠病（IBD）患者中半乳糖凝集素-3的表达水平相当。在正常黏膜中，半乳糖凝集素-3蛋白主要在分化的肠上皮细胞中观察到，优先位于基底外侧。然而，IBD患者炎症活检组织中半乳糖凝集素-3明显下调。用肿瘤坏死因子对未发炎的活检组织进行体外刺激导致半乳糖凝集素-3信使核糖核酸下调，与体内情况相似。分析外周血单个核细胞（PBMC）时，半乳糖凝集素-3主要由单核细胞产生。有丝分裂原刺激后，在存在半乳糖凝集素-3特异性小干扰RNA的情况下，我们观察到外周血T细胞增殖增加，活化诱导的细胞死亡减少。相反，外源性添加重组半乳糖凝集素-3导致有丝分裂原刺激的外周血T细胞增殖减少。
我们的结果表明，炎症黏膜中上皮半乳糖凝集素-3的下调反映了正常的免疫后果，而在非炎症条件下，其组成性表达可能有助于预防对共生细菌或食物成分的不适当免疫反应。因此，半乳糖凝集素-3可能对控制疾病活动具有重要价值。
