Polymeric binders suppress gliadin-induced toxicity in the intestinal epithelium.
OBJECTIVE
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.
Pinier
Maud
M
Faculty of Pharmacy, University of Montreal, Montreal, Canada.
Verdu
Elena F
EF
Nasser-Eddine
Mohamad
M
David
Chella S
CS
Vézina
Anne
A
Rivard
Nathalie
N
Leroux
Jean-Christophe
JC
D000818:Animals; D018938:Caco-2 Cells; D003599:Cytoskeleton / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects; D005903:Gliadin / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008689:Methacrylates / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000032:analysis; D011108:Polymers / Q000378:metabolism / Q000494:pharmacology*; D013451:Sulfonic Acids / Q000378:metabolism / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D008689:Methacrylates; D010750:Phosphoproteins; D011108:Polymers; D013451:Sulfonic Acids; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C005044:hydroxyethyl methacrylate; D005903:Gliadin; C077114:styrenesulfonic acid polymer