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

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.
AuthorsFlorian Obermeier, Nadja Dunger, Ludwig Deml, Hans Herfarth, Jürgen Schölmerich, Werner Falk
JournalEuropean journal of immunology (Eur J Immunol) Vol. 32 Issue 7 Pg. 2084-92 (Jul 2002) ISSN: 0014-2980 [Print] Germany
PMID12115630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Cytokines
  • DNA, Bacterial
  • Lipopolysaccharides
  • Oligodeoxyribonucleotides
  • Interferon-gamma
  • Dextran Sulfate
Topics
  • Acute Disease
  • Adjuvants, Immunologic (pharmacology)
  • Animals
  • Chronic Disease
  • Colitis (chemically induced, drug therapy, immunology)
  • CpG Islands (immunology)
  • Cytokines (secretion)
  • DNA, Bacterial (immunology)
  • Dextran Sulfate (adverse effects)
  • Disease Models, Animal
  • Female
  • Interferon-gamma (immunology)
  • Lipopolysaccharides (immunology, pharmacology)
  • Lymph Nodes (drug effects, immunology)
  • Mesentery
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Oligodeoxyribonucleotides (immunology, pharmacology)
  • Spleen (cytology, drug effects, immunology)
  • Th1 Cells (drug effects, immunology)
  • Th2 Cells (drug effects, immunology)
  • Tumor Cells, Cultured

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