Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease
Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease
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DOI：
10.1053/j.gastro.2007.01.030
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发表时间：
2007-04-01
期刊：
影响因子：
29.4
通讯作者：
Esposito, Carla
中科院分区：
文献类型：
--
作者：
Barone, Maria V.;Caputo, Ivana;Esposito, Carla
背景与目的：组织转谷氨酰胺酶(TTG)自身抗体是乳糜泻的标志物，该酶在许多重要的生物学过程中都是必需的。这项研究的目的是确定这些自身抗体是否参与了典型的乳糜泻黏膜病变的发病机制。方法：应用罗丹明标记的鬼臼乙素染色，我们评估了来自于乳糜泻患者的商用和克隆的tTG抗体是否会引起Caco-2、MCF7和NIH3T3细胞的细胞骨架改变。我们监测细胞水平的溴脱氧尿嘧啶核苷掺入，以确定tTG自身抗体是否能够诱导NIH3T3成纤维细胞和粘膜上皮细胞进入S期。结果：经tTG抗体处理后，Caco-2、MCF7和NIH3T3细胞的膜褶皱程度呈剂量依赖性增加。还可剂量依赖性地诱导GO同步化的NIH3T3成纤维细胞进入S期，但不影响细胞凋亡率。同样，tTG抗体诱导培养的乳糜泻患者的肠道活检标本中的上皮细胞进入S期。它们不影响来自非乳糜泻患者的活检标本。结论：tTG自身抗体通过与细胞外膜结合的谷氨酰胺转氨酶相互作用，可能在乳糜泻上皮细胞增殖中发挥重要作用。
Background & Aims: Tissue transglutaminase (tTG) autoantibodies are markers of celiac disease, and the enzyme is required for several crucial biological processes. The aim of this study was to determine whether these autoantibodies are involved in the pathogenesis of the mucosal lesion typical of celiac disease. Methods: Using rhodamine-conjugated phalloidin staining, we evaluated whether tTG antibodies, both commercially available and cloned from patients with celiac disease, cause cytoskeletal changes in Caco-2, MCF7, and NIH 3T3 cells. We monitored cell levels of bromodeoxyuridine incorporation to determine whether tTG autoantibodies are able to induce NIH 3T3 fibroblasts and epithelial mucosal cells into S phase. Results: Treatment with tTG antibodies caused a dose-dependent increase of membrane ruffling in Caco-2, MCF7, and NIH 3T3 cells. It also dose-dependently induced Go-synchronized NIH 3T3 fibroblasts into S phase but did not affect the rate of apoptosis. Similarly, tTG antibodies induced S-phase entry of epithelial cells in cultured intestinal biopsy specimens from patients with celiac disease. They did not affect biopsy specimens from patients without celiac disease. Conclusions: Our results suggest that tTG autoantibodies per se, by interacting with the extracellular membrane-bound transglutaminase, may play an important role in epithelial cell proliferation in celiac disease.