Paul, Gisela and Bataille, Frauke and Obermeier, Florian and Bock, Juergen and Klebl, Frank and Strauch, Ulrike and Lochbaum, Diane and Ruemmele, Petra and Farkas, Stefan and Schoelmerich, Juergen and Fleck, Martin and Rogler, Gerhard and Herfarth, Hans (2005) Analysis of intestinal haem-oxygenase-1 (HO-1) in clinical and experimental colitis. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 140 (3). pp. 547-555. ISSN 0009-9104, 1365-2249
Full text not available from this repository. (Request a copy)Abstract
Haem-oxygenase-1 (HO-1) has been shown to exert anti-inflammatory, anti-apoptotic and anti-proliferative effects. We investigated HO-1 expression in patients with inflammatory bowel disease (IBD) and could demonstrate a scattered expression of HO-1 in the intestinal epithelium of severely inflamed colonic mucosa of patients with IBD compared to control specimens such as diverticulitis, suggesting dysregulated expression in IBD. To further analyse potential mechanisms of HO-1 induction in the intestine we employed an in vitro epithelial cell apoptosis model and an experimental colitis model. In vitro induction of HO-1 by the HO-1 inducer cobalt protoporphyrin (CoPP) resulted in a dose-dependent down-regulation of caspase-3 activation in HT-29 cells, indicating an anti-apoptotic function of HO-1 in the intestine. In vivo, preventive HO-1 induction by CoPP in acute dextran sodium sulphate (DSS)-induced colitis led to a significant down-regulation of colonic inflammation (P < 0.01) with a concomitant reduction in interferon (IFN)-gamma - but unaffected interleukin (IL)-10-secretion by isolated mesenteric lymph nodes (P < 0.01). Additionally, TUNEL staining of colonic sections demonstrated fewer apoptotic epithelial cells in the colon of CoPP treated animals. No beneficial effects were observed if HO-1 was induced by CoPP after the onset of acute colitis or in chronic DSS-induced colitis. In conclusion, the data suggest a protective role of HO-1 if it is induced before the onset of inflammation. However, as shown by the lack of effects in established acute or in chronic colitis, the induction of HO-1 may not be a promising approach for the treatment of IBD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; SODIUM-INDUCED COLITIS; HEME OXYGENASE-1 INDUCTION; CARBON-MONOXIDE; ISCHEMIA/REPERFUSION INJURY; LUNG INJURY; (DSS)-INDUCED COLITIS; COLONIC INFLAMMATION; PROVIDES PROTECTION; IMPROVED SURVIVAL; apoptosis; Crohn's disease; HO-1; inflammatory bowel disease; ulcerative colitis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 May 2021 11:57 |
| Last Modified: | 10 May 2021 11:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36033 |
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