title: Oral treatment with SEW2871, a sphingosine-1-phosphate type 1 receptor agonist, ameliorates experimental colitis in interleukin-10 gene deficient mice.
abstract: SEW2871, a selective sphingosine-1-phosphate type 1 receptor (S1P1) agonist, has been shown to be effective in protecting kidneys against ischaemia-reperfusion injury by reducing CD4(+) T cell infiltration in mice. However, the effects of SEW2871 on colitis remain unclear. The aim of this study was to investigate the effects of SEW2871 on established colitis in interleukin (IL)-10 gene-deficient (IL-10(-/-)) mice, a murine model of Crohn's disease (CD). SEW2871 was administered by gavage at a dose of 20 mg/kg/day for 2 weeks to IL-10(-/-) mice. Severity of colitis, serum amyloid A, tissue myeloperoxidase (MPO), T cells in blood and colon lamina propria (LP) and proinflammatory cytokine productions were evaluated. Furthermore, the phospho-signal transducer and activator of transcription (STAT)-3 (p-STAT-3) expression in lymphocytes isolated from colon LP was also assessed. The 2-week administration of SEW2871 ameliorated established colitis in IL-10(-/-) mice, associated with a reduction of serum amyloid A concentration, a decreased colon MPO concentration, a depletion of the peripheral CD4(+) CD45(+) T cells and a reduction of the homing of T cells into colon LP. Moreover, typical cytokines of T helper type 1 (Th1) and Th17 cells and p-STAT-3 expression were also suppressed by SEW2871 treatment. SEW2871 treatment ameliorates established experimental colitis in IL-10(-/-) mice, which may provide a new therapeutic approach for human CD therapy.
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Zuo
authors.forename: W
authors.initials: W
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Gong
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010069:Oxadiazoles / Q000008:administration & dosage* / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D013876:Thiophenes / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid; C503964:SEW2871; D050796:STAT3 Transcription Factor; D000685:Serum Amyloid A Protein; D013876:Thiophenes; D016753:Interleukin-10; D009195:Peroxidase
keywords: Crohn's disease; IL-10 deficient mice; SEW2871; inflammation; treatment