Polymeric binders suppress gliadin-induced toxicity in the intestinal epithelium

Gastroenterology. 2009 Jan;136(1):288-98. doi: 10.1053/j.gastro.2008.09.016. Epub 2008 Sep 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Membrane Proteins
  • Methacrylates
  • Phosphoproteins
  • Polymers
  • Sulfonic Acids
  • TJP1 protein, human
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein
  • hydroxyethyl methacrylate
  • Gliadin
  • styrenesulfonic acid polymer