CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice

Obermeier, Florian and Dunger, Nadja and Deml, Ludwig and Herfarth, Hans and Schoelmerich, Juergen and Falk, Werner (2002) CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice. EUROPEAN JOURNAL OF IMMUNOLOGY, 32 (7). pp. 2084-2092. ISSN 0014-2980

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Abstract

Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal immune response with elevated levels of the. Th1 cytokines TNF, IL-12 and IFN-gamma. The luminal flora has been implicated as a major factor contributing to the initiation and perpetuation of chronic intestinal inflammation by as yet unknown mechanisms. Bacterial DNA contains unmethylated cytosine-guanosine dinucleotides (CpG) which strongly activate Th1-mediated immune responses. To test whether these CpG-motifs contribute to intestinal inflammation we treated mice with dextran-sulfate-sodium (DSS)-induced acute or chronic colitis for 5 days with CpG-containing oligodeoxynucleotides (CpG-ODN). Colonic inflammation was assessed by histological scoring. Colonic cytokine RNA was quantified by reverse transcription-PCR and cytokine secretion from mesenterial lymph node cells by ELISA. In chronic colitis, CpG-ODN treatment severely aggravated inflammation by 50%. Colonic expression of IFN-gamma and TNF was elevated (200- and 150-fold, respectively) and IFN-gamma and IL-12 secretion from lymph node cells was increased 5,000- and 8-fold, respectively, compared to GpG-ODN-treated controls. Similar effects were obtained in acute colitis. In conclusion, CpG-motifs; of bacterial DNA have proinflammatory activity by strengthening the Th1 arm of immunity in DSS-induced colitis, and might therefore play a significant role in the initiation and perpetuation of inflammation in IBD.

Item Type: Article
Uncontrolled Keywords: RESIDENT INTESTINAL FLORA; TUMOR-NECROSIS-FACTOR; CROHNS-DISEASE; ENTERIC MICROFLORA; ULCERATIVE-COLITIS; MURINE COLITIS; T-CELLS; PERMEABILITY; INFLAMMATION; ACTIVATION; experimental colitis; dextran sulfate sodium; CpG motif; bacterial DNA
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 18 Oct 2021 11:28
Last Modified: 18 Oct 2021 11:28
URI: https://pred.uni-regensburg.de/id/eprint/40109

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