Obermeier, Florian and Dunger, Nadja and Strauch, Ulrike G. and Hofmann, Claudia and Bleich, A. and Grunwald, Nicole and Hedrich, H. J. and Aschenbrenner, Elisabeth and Schlegelberger, B. and Rogler, Gerhard and Schoelmerich, Juergen and Falk, Werner (2005) CpG motifs of bacterial DNA essentially contribute to the perpetuation of chronic intestinal inflammation. GASTROENTEROLOGY, 129 (3). pp. 913-927. ISSN 0016-5085,
Full text not available from this repository. (Request a copy)Abstract
Background & Aims: Recently, we demonstrated a proinflammatory effect of cytosin-guanosin dinucleotide (CpG)-oligodeoxynucleotide (ODN) treatment in established dextran sulphate sodium (DSS)-induced colitis. Here, we investigated whether DNA derived from luminal bacteria plays a role in the perpetuation of chronic intestinal inflammation. Methods: Toll-like receptor (TLR9)-deficient and wild-type (wt) control mice were used for the induction of chronic DSS colitis. Moreover, mice with established chronic colitis using different experimental models were treated with adenoviral ODN (AV-ODN) known to block CpG effects. Colonic inflammation was scored and cytokine production was quantified both in colonic tissue and draining mesenteral lymph node cells (MILC). Results : Eight weeks after induction of chronic DSS colitis in TLR9-deficient mice, intestinal inflammation was significantly lower (-68%), and proinflammatory cytokine production was drastically reduced. Treatment of wt mice with chronic DSS-induced colitis with AV-ODN resulted in a significant amelioration of disease with a reduced histologic score (-43%) and reduced cytokine production of MLC (interleukin [IL]-6: -68%; interferon [IFN]-gamma: -48%) and RNA expression of the T helper (Th)1-specific transcription factor T-bet (-62%) in colonic tissue. Qualitatively, the same results were obtained in the severe combined immunodeficiency disease (SCID) transfer model of colitis and in spontaneous colitis in IL-10-deficient mice. Conclusions: Bacteria[ DNA derived from luminal bacteria contributes significantly to the perpetuation of chronic intestinal inflammation. Inhibition of the immune-stimulating properties of bacterial DNA using AVODN may offer a novel and specific tool for the treatment of inflammatory bowel disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEXTRAN SULFATE SODIUM; CD4(+) T-CELLS; INTERLEUKIN 10-DEFICIENT MICE; NORMAL LUMINAL BACTERIA; IFN-GAMMA PRODUCTION; NF-KAPPA-B; EXPERIMENTAL COLITIS; EPITHELIAL-CELLS; INTERFERON-GAMMA; MURINE COLITIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Apr 2021 12:34 |
| Last Modified: | 27 Apr 2021 12:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35687 |
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