期刊
GASTROENTEROLOGY
卷 136, 期 1, 页码 288-298出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2008.09.016
关键词
-
资金
- Canadian Celiac Association
- Fonds Quebecols de la Recherche sur la Nature et les Technologies
- Canadian Institutes of Health Research
- National Institutes of Health [DK 071003]
- CAG/CIHR New Investigator Establishment Award
- Canada Research Chair program
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK071003, R56DK071003] Funding Source: NIH RePORTER
Background & Aims: Celiac disease is a prevalent immune disorder caused by the ingestion of gliadin-containing grains. We investigated the ability of a polymeric binder to reverse the toxic effects induced by gliadin in human intestinal cells and gliadin-sensitive HCD4-DQ8 mice. Methods: Gliadin was neutralized by complexation to a linear copolymer of hydroxyethylmethacrylate (HEMA) and sodium 4-styrene sulfonate (SS). The ability of the polymeric binder to abrogate the damaging effect of gliadin on cell-cell contact was investigated in IEC-6, Caco-2/15, and primary cultured differentiated enterocytes. The efficacy of the polymeric binder in preventing gliadin-induced intestinal barrier dysfunction was assessed using gliadin-sensitive HLA-HCD4/DQ8 transgenic mice. Results: Poly(hydroxyethylmethacrylate-co-styrene sulfonate) [P(HEMA-co-SS)] complexed with gliadin in a relatively specific fashion. Intestinal cells exposed to gliadin underwent profound alterations in morphology and cell-cell contacts. These changes were averted by complexing the gliadin with P(HEMA-co-SS). More importantly, the P(HEMA-co-SS) hindered the digestion of gliadin by gastrointestinal enzymes, thus minimizing the formation of immunogenic peptides. Coadministration of P(HEMA-co-SS) with gliadin to HLA-HCD4/DQ8 mice attenuated gliadin-induced changes in the intestinal barrier and reduced intraepithelial lymphocyte and macrophage cell counts. Conclusions: Polymeric binders can prevent in vitro gliadin-induced epithelial toxicity and intestinal barrier dysfunction in HCD4/DQ8 mice. They have a potential role in the treatment of patients with gluten-induced disorders.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据