title: Secreted protein acidic and rich in cysteine (SPARC) exacerbates colonic inflammatory symptoms in dextran sodium sulphate-induced murine colitis.
abstract: BACKGROUND
  Secreted Protein Acidic and Rich in Cysteine (SPARC) is expressed during tissue repair and regulates cellular proliferation, migration and cytokine expression. The aim was to determine if SPARC modifies intestinal inflammation.
  
  
  METHODS
  Wild-type (WT) and SPARC-null (KO) mice received 3% dextran sodium sulphate (DSS) for 7 days. Inflammation was assessed endoscopically, clinically and histologically. IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-12/IL23p40, TNF-α, IFN-γ, RANTES, MCP-1, MIP-1α, MIP-1β, MIG and TGF-β1 levels were measured by ELISA and cytometric bead array. Inflammatory cells were characterised by CD68, Ly6G, F4/80 and CD11b immunofluorescence staining and regulatory T cells from spleen and mesenteric lymph nodes were assessed by flow cytometry.
  
  
  RESULTS
  KO mice had less weight loss and diarrhoea with less endoscopic and histological inflammation than WT animals. By day 35, all (n = 13) KO animals completely resolved the inflammation compared to 7 of 14 WT mice (p<0.01). Compared to WTs, KO animals at day 7 had less IL1β (p= 0.025) and MIG (p = 0.031) with higher TGFβ1 (p = 0.017) expression and a greater percentage of FoxP3+ regulatory T cells in the spleen and draining lymph nodes of KO animals (p<0.01). KO mice also had fewer CD68+ and F4/80+ macrophages, Ly6G+ neutrophils and CD11b+ cells infiltrating the inflamed colon.
  
  
  CONCLUSIONS
  Compared to WT, SPARC KO mice had less inflammation with fewer inflammatory cells and more regulatory T cells. Together, with increased TGF-β1 levels, this could aid in the more rapid resolution of inflammation and restoration of the intestinal mucosa suggesting that the presence of SPARC increases intestinal inflammation.
authors.affiliation: Centre for Inflammatory Bowel Diseases, School of Medicine and Pharmacology, University of Western Australia, Fremantle, Western Australia, Australia ; School of Veterinary and Biomedical Sciences, Murdoch University, Perth, Western Australia, Australia.
authors.forename: Yoke-Leng
authors.initials: YL
authors.lastname: Ng
authors.forename: Borut
authors.initials: B
authors.lastname: Klopcic
authors.forename: Frances
authors.initials: F
authors.lastname: Lloyd
authors.forename: Cynthia
authors.initials: C
authors.lastname: Forrest
authors.forename: Wayne
authors.initials: W
authors.lastname: Greene
authors.forename: Ian C
authors.initials: IC
authors.lastname: Lawrance
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects*; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D016207:Cytokines; D015676:Osteonectin; C578250:SPARC protein, mouse; D016264:Dextran Sulfate