title: Beneficial effect of glatiramer acetate treatment on syndecan-1 expression in dextran sodium sulfate colitis.
abstract: Syndecan-1, the most abundant heparan sulfate proteoglycan in the gastrointestinal tract, is reduced in the regenerative epithelium in inflammatory bowel disease (IBD). This study explored the effects of the immunomodulator glatiramer acetate (GA; Copaxone) treatment on syndecan-1 expression in dextran sodium sulfate (DSS)-induced colitis. Acute and chronic colitis was induced in C57BL/6 mice by 2 and 1.5% DSS in tap water, respectively. GA was applied subcutaneously, 2 mg per mouse per day, starting on the day of DSS induction until the mice were sacrificed. Syndecan-1 expression was assessed by immunohistochemistry. The effect of adoptive transfer of GA-specific T cells as an organ-specific therapy also was evaluated. Syndecan-1 expression was significantly lower in both colitis groups compared with that in naive mice (p < 0.0001). GA attenuated clinical scores and pathological manifestations of colitis and led to the reinstatement of normal levels of syndecan-1. After adoptive transfer, GA-specific cells homed to the surface epithelium of the distal colon, accompanied by the augmentation of syndecan-1 staining in their vicinity. We concluded that syndecan-1 expression is reduced in DSS-induced colitis and could be a potential prognostic factor in IBD. Treatment with GA exerts not only an anti-inflammatory effect but also a possible beneficial effect in stabilizing the intestinal epithelium barrier and tissue repair in DSS colitis. GA may be applied as a novel drug for IBD, shifting treatment from immunosuppression toward immunomodulation.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Yablecovitch
authors.forename: Maytal
authors.initials: M
authors.lastname: Shabat-Simon
authors.forename: Rina
authors.initials: R
authors.lastname: Aharoni
authors.forename: Raya
authors.initials: R
authors.lastname: Eilam
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.forename: Ruth
authors.initials: R
authors.lastname: Arnon
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002432:Cecum / Q000473:pathology; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D005260:Female; D000068717:Glatiramer Acetate; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000627:therapeutic use*; D053668:Syndecan-1 / Q000096:biosynthesis*
chemical_list: D000893:Anti-Inflammatory Agents; D010455:Peptides; D053668:Syndecan-1; D000068717:Glatiramer Acetate; D016264:Dextran Sulfate