title: Phosphorylcholine-tuftsin compound prevents development of dextransulfate-sodium-salt induced murine colitis: implications for the treatment of human inflammatory bowel disease.
abstract: Improved clinical findings of inflammatory bowel disease (IBD) upon treatment with helminthes and their ova were proven in animal models of IBD and in human clinical studies. The immunomodulatory properties of several helminthes were attributed to the phosphorylcholine (PC) molecule. We assessed the therapeutic potential of tuftsin-PC conjugate (TPC) to attenuate murine colitis. Colitis was induced by Dextransulfate-Sodium-Salt (DSS) in drinking water. TPC was given by daily oral ingestion (50 μg/0.1 ml/mouse or PBS) starting at day -2. Disease activity index (DAI) score was followed daily and histology of the colon was performed by H&E staining. Analysis of the cytokines profile in distal colon lysates was performed by immunoblot. Treatment of DSS induced colitis with TPC prevented the severity of colitis, including a reduction in the DAI score, less shortening of the colon and less inflammatory activity in histology. The immunoblot showed that the colitis preventive activity of TPC was associated with downregulation of colon pro-inflammatory IL-1β, TNFα and IL-17 cytokines expression, and enhancement of anti-inflammatory IL-10 cytokine expression. In the current study, we demonstrated that TPC treatment can prevent significantly experimental colitis induction in naïve mice. We propose the TPC as a novel potential small synthetic molecule to treat colitis.
authors.affiliation: Department of Gastroenterology, Sheba Medical Center affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Ben-Ami Shor
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Bashi
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Jordan
authors.initials: J
authors.lastname: Lachnish
authors.affiliation: Department of Organic Chemistry, The Weizmann Institute of Sciences, Rehovot, Israel.
authors.forename: Mati
authors.initials: M
authors.lastname: Fridkin
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Bizzaro
authors.affiliation: Institute of Pathology, Sheba Medical Center, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshak
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Blank
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel; Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel-Aviv University, Israel. Electronic address: shoenfel@post.tau.ac.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010767:Phosphorylcholine; D012720:Severity of Illness Index; D014405:Tuftsin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D010767:Phosphorylcholine; D016264:Dextran Sulfate; D014405:Tuftsin
keywords: Colitis; Helminthes; Inflammatory bowel disease; Phosphorylcholine; Tuftsin; Worms