Osteopontin attenuation of dextran sulfate sodium-induced colitis in mice

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...

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Bibliographic Details
Published in:Laboratory investigation 2009-10, Vol.89 (10), p.1169-1181
Main Authors: da Silva, Andre Paes Batista, Ellen, Richard P, Sørensen, Esben S, Goldberg, Harvey A, Zohar, Ron, Sodek, Jaro
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biotechnology
colitis
Colitis - chemically induced
Colitis - drug therapy
Colitis - immunology
Colitis - metabolism
Colon - immunology
Colon - metabolism
cytokines
Dextran Sulfate - toxicity
Fundamental and applied biological sciences. Psychology
Inflammation Mediators - metabolism
innate immunity
Investigative techniques, diagnostic techniques (general aspects)
Laboratory Medicine
Macrophages - drug effects
Male
Medical sciences
Medicine
Medicine & Public Health
Mice
Mice, Inbred C57BL
Mice, Knockout
Milk - chemistry
murine
Neutrophils - drug effects
osteopontin
Osteopontin - analysis
Osteopontin - pharmacokinetics
Osteopontin - therapeutic use
Pathology
Recombinant Proteins - therapeutic use
research-article
Serum Albumin, Bovine - therapeutic use
Transforming Growth Factor beta1 - metabolism
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Summary: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 2 μg/ml bovine milk OPN, dissolved in drinking water, was given to mice 24 h 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
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.2009.80