title: CpG motifs of bacterial DNA essentially contribute to the perpetuation of chronic intestinal inflammation.
abstract: OBJECTIVE
  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 (MLC).
  
  
  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
  Bacterial DNA derived from luminal bacteria contributes significantly to the perpetuation of chronic intestinal inflammation. Inhibition of the immune-stimulating properties of bacterial DNA using AV-ODN may offer a novel and specific tool for the treatment of inflammatory bowel disease.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Florian.Obermeier@klinik.uni-regensburg.de
authors.forename: Florian
authors.initials: F
authors.lastname: Obermeier
authors.forename: Nadja
authors.initials: N
authors.lastname: Dunger
authors.forename: Ulrike G
authors.initials: UG
authors.lastname: Strauch
authors.forename: Claudia
authors.initials: C
authors.lastname: Hofmann
authors.forename: Andre
authors.initials: A
authors.lastname: Bleich
authors.forename: Nicole
authors.initials: N
authors.lastname: Grunwald
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hedrich
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Aschenbrenner
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Werner
authors.initials: W
authors.lastname: Falk
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000150:complications; D001483:Base Sequence; D003092:Colitis / Q000188:drug therapy*; D017931:DNA Primers; D004269:DNA, Bacterial / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D015226:Dinucleoside Phosphates / Q000032:analysis* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9
chemical_list: D017931:DNA Primers; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; C015772:CpG dinucleotide