title: Indomethacin and retinoic acid modify mouse intestinal inflammation and fibrosis: a role for SPARC.
abstract: The mouse model of 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-induced intestinal fibrosis allows for detailed study of the extracellular matrix changes that complicate Crohn's disease. Indomethacin induces intestinal fibrosis, while retinoic acid (RA) reduces liver fibrosis. Secreted protein acidic and rich in cysteine (SPARC), an extracellular matrix-modifying agent, may potentially link these opposing effects. Our aim was to determine the effects of indomethacin and RA and to evaluate their correlation to SPARC expression in the TNBS mouse model. CD-1 mice were randomised to TNBS enemas weekly for 2 or 8 weeks with or without indomethacin (0.2 mg/kg per day) or RA (100 microg/kg per day). At 2 weeks, indomethacin/TNBS enhanced and RA reduced inflammation, tissue destruction and fibrosis. The expression of SPARC was inversely related to fibrosis, but not to inflammation, in the TNBS-alone groups at 2 weeks; these differences were lost by 8 weeks. The results demonstrate that indomethacin increases TNBS-induced fibrosis in mice, while RA reduces it, and that SPARC may link these opposing effects.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle, WA, Australia.
authors.forename: Borut
authors.initials: B
authors.lastname: Klopcic
authors.forename: Amber
authors.initials: A
authors.lastname: Appelbee
authors.forename: Warren
authors.initials: W
authors.lastname: Raye
authors.forename: Frances
authors.initials: F
authors.lastname: Lloyd
authors.forename: James C I
authors.initials: JC
authors.lastname: Jooste
authors.forename: Cynthia Heather
authors.initials: CH
authors.lastname: Forrest
authors.forename: Ian Craig
authors.initials: IC
authors.lastname: Lawrance
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000494:pharmacology*; D051379:Mice; D015676:Osteonectin / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014212:Tretinoin / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D015676:Osteonectin; C524549:SMOC-1 protein, mouse; D014212:Tretinoin; D012313:RNA; D014302:Trinitrobenzenesulfonic Acid; D007213:Indomethacin