Rescue from Inflammatory Destruction in Experimental Colitis by Osteopontin Administration

Background: Osteopontin (OPN) is a matricellular cytokine present in most tissues and body fluids that is required for proper immune responses. Our studies using an experimental acute colitis model in the OPN-null (-/-) mouse found exacerbated tissue destruction and reduced repair in comparison to wild-type (WT) controls. Destruction of gut tissues was associated with increased neutrophils activity, reduced cell survival, and reduced secretion of inflammatory cytokines such as TNF-á and TGF-â1. Since OPN is normally present in milk, we hypothesize that dairy derived OPN may have a role in protecting the intestines from the adverse effects of inflammatory colitis. Objective: To analyze the ability of purified milk OPN dissolved in drinking water to subdue aggravated inflammation in the dextran sulfate sodium (DSS) colitis model. Methods: Purified bovine milk OPN dissolved in the drinking water in either physiological (HD) or 10-fold lower (LD) concentration was given to mice 24 hours prior to administration of the DSS to induce colitis. Clinical parameters and neutrophil functions were analyzed as previously reported ( J Cell Physiol 208:629, 2006). Results: HD-OPN significantly reduced disease activity indices (DAI) in DSS WT and OPN-/- mice. HD-treated DSS WT exhibited 37% less weight loss, reduced colon shortening, spleen enlargements, improved blood RBC counts and reduced gut neutrophil activity as shown by myeloperoxidase activity (P<0.05). Similar effects were found for DSS OPN-/- mice treated with HD-OPN but to a lesser degree than those found for WT. Conclusions: Physiological concentrations of dairy OPN dissolved in drinking water can improve the host response to DSS acute colitis.

Supported by grants ITM-83267 and 300360 from the Canadian Institutes of Health Research (CIHR) and the Dairy Farmers Foundation of Canada (JS, RZ, HG), and CIHR training fellowship STP-53877 and Harron Scholarship (APBS).