Abstract | OBJECTIVE: DESIGN: Chronic colitis was induced by administration of 2% dextran sodium sulphate (DSS) in distilled water. Mice were assessed for disease severity, histopathology and endoscopic appearance. Furthermore, DSS-exposed Ctsk(-/-) mice were treated by rectal administration of recombinant cathepsin K. Intestinal microflora was assessed by real-time PCR and 16srDNA molecular fingerprinting of ileal and colonic mucosal and faecal samples. RESULTS: Using Ctsk(-/-) mice, the authors demonstrate a protective role of cathepsin K against chronic DSS colitis. Dissecting the underlying mechanisms the authors found cathepsin K to be present in intestinal goblet cells and the mucin layer. Furthermore, a direct cathepsin K-mediated bactericidal activity against intestinal bacteria was demonstrated, which potentially explains the alteration of intestinal microbiota observed in Ctsk(-/-) mice. Rectal administration of recombinant cathepsin K in DSS-treated Ctsk(-/-) mice ameliorates the severity of intestinal inflammation. CONCLUSION:
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Authors | Christian Sina, Simone Lipinski, Olga Gavrilova, Konrad Aden, Ateequr Rehman, Andreas Till, Andrea Rittger, Rainer Podschun, Ulf Meyer-Hoffert, Robert Haesler, Emilie Midtling, Katrin Pütsep, Michael A McGuckin, Stefan Schreiber, Paul Saftig, Philip Rosenstiel |
Journal | Gut
(Gut)
Vol. 62
Issue 4
Pg. 520-30
(Apr 2013)
ISSN: 1468-3288 [Electronic] England |
PMID | 22442160
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dextran Sulfate
- Cathepsin K
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Topics |
- Animals
- Blotting, Western
- Cathepsin K
(metabolism, pharmacology)
- Colitis
(chemically induced, drug therapy, microbiology, pathology)
- Dextran Sulfate
- Disease Models, Animal
- Endoscopy, Gastrointestinal
- Enzyme-Linked Immunosorbent Assay
- Immunohistochemistry
- Mice
- Mice, Inbred C57BL
- Real-Time Polymerase Chain Reaction
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