Polymeric binders suppress gliadin-induced toxicity in the intestinal epithelium

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 136; no. 1; p. 288
• Main Authors: Pinier, Maud, Verdu, Elena F, Nasser-Eddine, Mohamad, David, Chella S, Vézina, Anne, Rivard, Nathalie, Leroux, Jean-Christophe
• Format: Journal Article
• Language: English
• Published: United States 01.01.2009
• Subjects: Animals; Caco-2 Cells; Cytoskeleton - drug effects; Enterocytes - drug effects; Gliadin - metabolism; Gliadin - toxicity; Humans; Intestinal Mucosa - drug effects; Male; Membrane Proteins - analysis; Methacrylates - metabolism; Methacrylates - pharmacology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Phosphoproteins - analysis; Polymers - metabolism; Polymers - pharmacology; Sulfonic Acids - metabolism; Sulfonic Acids - pharmacology; Zonula Occludens-1 Protein
• ISSN: 1528-0012
• DOI: 10.1053/j.gastro.2008.09.016

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. 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. 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. 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.