title: Osteopontin deficiency protects mice from Dextran sodium sulfate-induced colitis.
abstract: BACKGROUND
  Osteopontin (OPN), a secreted glycoprotein that promotes TH1 immune responses, is involved in several inflammatory conditions. Recently, OPN plasma levels have been demonstrated to be elevated in patients with Crohn's disease. From this evidence, we investigated in the present study whether OPN deficiency protects mice against dextran sodium sulfate (DSS)-induced colitis.
  
  
  METHODS
  Colitis was induced in OPN -/- mice and matched wild-type Black Swiss control mice by adding 3.5% DSS to their drinking water. Disease progression was evaluated for 10 days by measuring body weight, stool consistency, rectal bleeding, colon lengths, histology, and immunohistochemistry. Levels of the acute-phase protein serum amyloid A, O PN, the proinflammatory cytokines interleukin (IL)-6 and IL-12, and the anti-inflammatory cytokine IL-10 were measured in the serum and, in the case of IL-10 and IL-12, in supernatants from colonic explants at the end of treatment.
  
  
  RESULTS
  After DSS treatment, OPN -/- mice exhibited significantly decreased disease activity compared with wild-type mice, as evidenced by reduced rectal bleeding, weight loss, and histological intestinal injury (P < 0.002). Furthermore, serum levels of serum amyloid A and IL-6 increased to a lesser extent (P < 0.001), which also was the case for the release of IL-12 by colonic explants (P < 0.01). The release of IL-10 by colonic explants, however, was increased (P < 0.01). Serum levels of IL-10 and IL-12 were not affected by DSS treatment in both wild-type and OPN-/- mice. Macrophage infiltration into inflamed colonic tissue also was markedly attenuated in DSS-treated OPN -/- mice compared with wild-type mice.
  
  
  CONCLUSIONS
  This study shows that OPN deficiency significantly protected mice from colitis by attenuating the TH1 response and macrophage chemotaxis. OPN may represent a novel attractive target for pharmacological treatment of inflammatory bowel disease.
authors.affiliation: Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY 40536-0084, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.forename: Erik R M
authors.initials: ER
authors.lastname: Eckhardt
authors.forename: Helieh S
authors.initials: HS
authors.lastname: Oz
authors.forename: Dennis
authors.initials: D
authors.lastname: Bruemmer
authors.forename: Willem J S
authors.initials: WJ
authors.lastname: de Villiers
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D016264:Dextran Sulfate; D051379:Mice; D008822:Mice, Transgenic; D053495:Osteopontin; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000172:deficiency*
chemical_list: D016207:Cytokines; D000685:Serum Amyloid A Protein; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D016264:Dextran Sulfate