Osteopontin as two-sided mediator of intestinal inflammation
| Autor: | Robert Sabat, Christian Sina, Kerstin Wolk, Elianne Tchatchou, Ute Hoffmann, Verena Moos, Katja Heilmann, Pamela Holzlöhner, Ursula Günthert, Stefan Schreiber, C Hayford, Martin Zeitz, Bianca M. Wittig, Ellen Witte, Christoph Loddenkemper |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Adolescent medicine.medical_treatment Inflammation Enzyme-Linked Immunosorbent Assay Biology Inflammatory bowel disease Mice Young Adult stomatognathic system Crohn Disease Phagocytosis inflammatory bowel disease medicine Animals Humans Osteopontin Colitis Acute colitis Aged Mice Knockout Mucous Membrane Th1 immune response Reverse Transcriptase Polymerase Chain Reaction Macrophages Dextran Sulfate Interleukin Cell Biology Articles Macrophage Activation Middle Aged medicine.disease Inflammatory Bowel Diseases Immunohistochemistry Mice Inbred C57BL Cytokine inflammation Immunology Acute Disease biology.protein Molecular Medicine Cytokines Tumor necrosis factor alpha medicine.symptom |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | 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 dextran sodium sulfate (DSS)-induced colitis. To identify the role of this mediator in intestinal inflammation, we analysed 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 interleukin (IL)-1 beta 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 tumour necrosis factor (TNF)-alpha, which could be due to systemically present lipopolysaccharide 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 whereas during chronic inflammation it promotes the Th1 response and strengthens inflammation. |
| Databáze: | OpenAIRE |
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