Indomethacin and retinoic acid modify mouse intestinal inflammation and fibrosis: a role for SPARC.
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.
Klopcic
Borut
B
School of Medicine and Pharmacology, University of Western Australia, Fremantle, WA, Australia.
Appelbee
Amber
A
Raye
Warren
W
Lloyd
Frances
F
Jooste
James C I
JC
Forrest
Cynthia Heather
CH
Lawrance
Ian Craig
IC
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
D015676:Osteonectin; C524549:SMOC-1 protein, mouse; D014212:Tretinoin; D012313:RNA; D014302:Trinitrobenzenesulfonic Acid; D007213:Indomethacin