Obermeier, Florian and Dunger, N. and Strauch, U. G. and Grunwald, N. and Herfarth, H. and Schoelmerich, Juergen and Falk, W. (2003) Contrasting activity of cytosin-guanosin dinucleotide oligonucleotides in mice with experimental colitis. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 134 (2). pp. 217-224. ISSN 0009-9104
Full text not available from this repository. (Request a copy)Abstract
Intestinal inflammation in inflammatory bowel disease (IBD) and experimental models of colitis is characterized by a dysregulated intestinal immune response with elevated levels of Th-1 cytokines. The luminal flora has been implicated as a major factor contributing to the initiation and perpetuation of inflammation in experimental colitis by mechanisms not known. Bacterial DNA contains unmethylated cytosin-guanosin dinucleotides (CpG) which strongly activate Th-1-mediated immune responses. To test whether these CpG-motifs modulate intestinal inflammation we treated mice with dextran sulphate sodium (DSS)-induced colitis with CpG-containing oligodeoxynucleotides (CpG-ODN). CpG-ODN given after the onset of DSS colitis aggravated the disease, as indicated by a significantly increased loss of body weight and a 30% increase of the histological score. Further, we found a severe increase of proinflammatory cytokines (interleukin (IL)-6: 40-fold; interferon (IFN)-gamma : 11-fold). In a pretreatment setting CpG-ODN reduced weight loss significantly and reduced intestinal inflammation by 45%. Colonic IFN-gamma and IL-6 mRNA levels were reduced by 75%, and IL-10 was elevated by 400% compared to controls. The prophylactic CpG-effect was not imitated by IL-12 because IL-12 pretreatment was not protective. In time-course experiments, CpG-ODN pretreatment over 5 days resulted in a tolerance effect concerning its IFN-gamma-inducing quality, and during the following days of colitis induction IL-10 secretion from mesenterial lymph node cells was elevated compared to controls. Therefore, the prophylactic effect of CpG-ODN might be explained by its tolerizing effect and/or the increased ability for IL-10 production during the consecutive intestinal inflammation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; BACTERIAL-DNA; CPG MOTIFS; ENTERIC MICROFLORA; MURINE COLITIS; LIPOPOLYSACCHARIDE; TOLERANCE; INTERLEUKIN-10; bacterial DNA; CpG motifs; dextran sulphate sodium; experimental colitis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Aug 2021 05:35 |
| Last Modified: | 30 Aug 2021 08:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38433 |
Actions (login required)
 |
View Item |
