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Osteopontin as two-sided mediator of intestinal inflammation

Heilmann, Katja and Hoffmann, Ute and Witte, Ellen and Loddenkemper, Christoph and Sina, Christian and Schreiber, Stefan and Hayford, Claudia and Holzlöhner, Pamela and Wolk, Kerstin and Tchatchou, Elianne and Moos, Verena and Zeitz, Martin and Sabat, Robert and Günthert, Ursula and Wittig, Bianca Maria. (2009) Osteopontin as two-sided mediator of intestinal inflammation. Journal of cellular and molecular medicine, Vol. 13, no. 6. pp. 1162-1174.

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Official URL: http://edoc.unibas.ch/dok/A5249197

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Abstract

Osteopontin (OPN) is characterized as a major amplifier of Th1-immune responses. However, its role in intestinal inflammation is currently unknown. We found considerably raised OPN levels in blood of wild-type (wt) mice with DSS-induced colitis. To identify the role of this mediator in intestinal inflammation, we analyzed experimental colitis in OPN deficient (OPN-/-) mice. In the acute phase of colitis these mice showed more extensive colonic ulcerations and mucosal destruction than WT mice, which was abrogated by application of soluble OPN. Within the OPN-/- mice, infiltrating macrophages were not activated and showed impaired phagocytosis. Reduced mRNA expression of IL-1beta and matrix metalloproteinases was found in acute colitis of OPN-/- mice. This was associated with decreased blood levels of IL-22, a Th17 cytokine that may mediate epithelial regeneration. However, OPN-/- mice showed increased serum levels of TNF-alpha, which could be due to systemically present LPS translocated to the gut. In contrast to acute colitis, during chronic DSS-colitis, which is driven by a Th1 response of the lamina propria infiltrates, OPN-/- mice were protected from mucosal inflammation and demonstrated lower serum levels of IL-12 than WT mice. Furthermore, neutralization of OPN in WT mice abrogated colitis. Lastly, we demonstrate that in patients with active Crohn's disease OPN serum concentration correlated significantly with disease activity. Taken together, we postulate a dual function of OPN in intestinal inflammation: During acute inflammation OPN seems to activate innate immunity, reduces tissue damage, and initiates mucosal repair while during chronic inflammation it promotes the Th1 response and strengthens inflammation.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
UniBasel Contributors:Günthert, Ursula
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Wiley-Blackwell
ISSN:1582-1838
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Sep 2015 14:31
Deposited On:22 Mar 2012 14:01

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