title: Preconditioning with intravenous colitic cell-free DNA prevents DSS-colitis by altering TLR9-associated gene expression profile.
abstract: BACKGROUND
  Presence of cell-free-circulating DNA (fcDNA) sequences in sera of patients with inflammatory bowel diseases (IBD) is a well-established phenomenon. Potential roles of fcDNA in diagnosis, prognosis and therapy monitoring of chronic inflammatory colonic disorders have already been examined, albeit its actual biological function still remains unclear.
  
  
  OBJECTIVE
  In the present experiment, we studied the immunobiological effects of isolated fcDNA of normal and inflammatory origin administered intravenously to mice prior to induction of dextran sulfate sodium (DSS)-colitis. In addition to evaluate the current disease and histological activity, changes of the gene expression profile in isolated lamina propria cells upon TLR9 ligation were assayed.
  
  
  RESULTS
  A single intravenous dose of fcDNA pretreatment with colitic fcDNA exhibited beneficial response concerning the clinical and histological severity of DSS-colitis as compared to effects of normal fcDNA. Pretreatment with colitic fcDNA substantially altered the expression of several TLR9-related and inflammatory cytokine genes in a clinically favorable manner.
  
  
  CONCLUSIONS
  During the process of acute colitis, the subsequent inflammatory environment presumably results in changes of fcDNA with the potential to facilitate the downregulation of inflammation and improvement of regeneration. Thus, preconditioning of mice with colitis-derived fcDNA via TLR9 signaling could exert a tissue-protective effect and influence beneficially the course of DSS-colitis. Elucidating mechanisms of immune response alterations by nucleic acids may provide further insight into the etiology of IBD and develop the basis of novel immunotherapies.
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi Street 46, Budapest, 1088, Hungary, muzes.gyorgyi@med.semmelweis-univ.hu.
authors.forename: Györgyi
authors.initials: G
authors.lastname: Műzes
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
authors.forename: István
authors.initials: I
authors.lastname: Fűri
authors.forename: Miklós
authors.initials: M
authors.lastname: Constantinovits
authors.forename: Sándor
authors.initials: S
authors.lastname: Spisák
authors.forename: Barnabás
authors.initials: B
authors.lastname: Wichmann
authors.forename: Gábor
authors.initials: G
authors.lastname: Valcz
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Béla
authors.initials: B
authors.lastname: Molnár
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000517:prevention & control*; D004247:DNA / Q000008:administration & dosage / Q000494:pharmacology*; D016264:Dextran Sulfate / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*
chemical_list: C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D004247:DNA; D016264:Dextran Sulfate