Research Article

Laboratory Investigation (2009) 89, 1169–1181; doi:10.1038/labinvest.2009.80; published online 10 August 2009

Osteopontin attenuation of dextran sulfate sodium-induced colitis in mice

Andre Paes Batista da Silva1,2, Richard P Ellen1,2, Esben S Sørensen3, Harvey A Goldberg4, Ron Zohar5 and Jaro Sodek1,2

  1. 1CIHR Group in Matrix Dynamics, University of Toronto, Toronto, ON, Canada
  2. 2Dental Research Institute, University of Toronto, Toronto, ON, Canada
  3. 3Department of Molecular Biology, University of Aarhus, Aarhus, Denmark
  4. 4CIHR Group in Skeletal Development and Remodeling, Department of Biochemistry, School of Dentistry, University of Western Ontario, London, ON, Canada
  5. 5Private Practice, Toronto, ON, Canada

Correspondence: CDr RP Ellen, Dental Research Institute, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, Canada M5G 1G6. E-mail: richard.ellen@dentistry.utoronto.ca

Received 20 March 2009; Revised 16 June 2009; Accepted 30 June 2009; Published online 10 August 2009.

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Abstract

Osteopontin (OPN) is a matricellular cytokine present in most tissues and body fluids; it is known to modulate immune responses. In previous studies using the dextran sulfate sodium (DSS) acute colitis model, we found exacerbated tissue destruction and reduced repair in OPN-null (−/−) mice compared with wild-type (WT) controls. As OPN is normally present in milk, we hypothesized that administration of OPN may protect the intestines from the adverse effects of experimental colitis. A volume of 20 or 2μg/ml bovine milk OPN, dissolved in drinking water, was given to mice 24h before, and during administration of DSS. Clinical parameters of colitis and neutrophil functions were analyzed as previously reported. Orally administered OPN was absorbed and detected in the colon mucosa by immunohistochemistry. The 20 μg/ml OPN- and DSS-treated WT mice showed 37% less weight loss and reduced colon shortening and spleen enlargements than control mice (P<0.05). OPN administration also reduced the disease activity index, improved red blood cell counts, and reduced gut neutrophil activity compared with the DSS-treated WT mice that were not administered OPN (P<0.05). Immunohistochemical detection of F4/80-labelled cells (macrophages) was also less frequent. The level of transforming growth factor β1 (TGF-β1) was increased and the levels of pro-inflammatory mediators decreased in colon tissue samples of OPN-treated mice analyzed by ELISA. The reversal of experimental colitis parameters by exogenous OPN was not as robust in the OPN/ mice. Administration of prokaryotic-expressed recombinant OPN and bovine serum albumin were ineffective. This study shows that administration of a physiological concentration of milk OPN in drinking water ameliorates the destructive host response in DSS-induced acute colitis.

Keywords:

colitis, cytokines, innate immunity, murine, osteopontin