Intravenous Administration of a Single-Dose Free-Circulating DNA of Colitic Origin Improves Severe Murine DSS-Colitis

F. Sípos, G. Müzes, István Fűri, S. Spisák, Barnabás Wichmann, Tiana M. Germann, Miklós Constantinovits, T. Krenács, Z. Tulassay, B. Molnár

Research output: Article

4 Citations (Scopus)

Abstract

In inflammatory bowel diseases the presence of free-circulating DNA (fcDNA) sequences in the sera is an established phenomenon, albeit its real biological function still remains unclear. In our study the immunobiologic effects of a single-dose, intravenously administered fcDNA of normal and colitic origin were assayed in DSS-colitic and control mice. In parallel with disease and histological activity evaluations changes of the TLR9 and inflammatory cytokine signaling gene expression profiles were assayed in isolated cells of the lamina propria. Intravenously administered colitis-derived fcDNA displayed a more prominent beneficial action regarding the clinical and histological severity of DSS-colitis than that of fcDNA of normal origin. Systemic administration of colitis-derived fcDNA significantly altered the expression of certain TLR9-related and proinflammatory cytokine genes in a clinically favorable manner. Presumably due to induction of severe colitis, the subsequent marked inflammatory environment may result changes in fcDNA with a potential to promote the downregulation of inflammation and improvement of tissue regeneration. Elucidating mechanisms of innate immune alterations by nucleic acids may provide further insight into the etiology of inflammatory bowel diseases, and develop the basis of novel nucleic acid-based immunotherapies.

Original languageEnglish
Pages (from-to)867-877
Number of pages11
JournalPathology and Oncology Research
Volume20
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

Colitis
Intravenous Administration
DNA
Inflammatory Bowel Diseases
Nucleic Acids
Cytokines
Transcriptome
Immunotherapy
Regeneration
Mucous Membrane
Down-Regulation
Inflammation
Serum
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

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title = "Intravenous Administration of a Single-Dose Free-Circulating DNA of Colitic Origin Improves Severe Murine DSS-Colitis",
abstract = "In inflammatory bowel diseases the presence of free-circulating DNA (fcDNA) sequences in the sera is an established phenomenon, albeit its real biological function still remains unclear. In our study the immunobiologic effects of a single-dose, intravenously administered fcDNA of normal and colitic origin were assayed in DSS-colitic and control mice. In parallel with disease and histological activity evaluations changes of the TLR9 and inflammatory cytokine signaling gene expression profiles were assayed in isolated cells of the lamina propria. Intravenously administered colitis-derived fcDNA displayed a more prominent beneficial action regarding the clinical and histological severity of DSS-colitis than that of fcDNA of normal origin. Systemic administration of colitis-derived fcDNA significantly altered the expression of certain TLR9-related and proinflammatory cytokine genes in a clinically favorable manner. Presumably due to induction of severe colitis, the subsequent marked inflammatory environment may result changes in fcDNA with a potential to promote the downregulation of inflammation and improvement of tissue regeneration. Elucidating mechanisms of innate immune alterations by nucleic acids may provide further insight into the etiology of inflammatory bowel diseases, and develop the basis of novel nucleic acid-based immunotherapies.",
keywords = "DSS-colitis, Free-circulating DNA, Proinflammatory cytokines, Tissue regeneration, Toll-like receptor 9",
author = "F. S{\'i}pos and G. M{\"u}zes and Istv{\'a}n Fűri and S. Spis{\'a}k and Barnab{\'a}s Wichmann and Germann, {Tiana M.} and Mikl{\'o}s Constantinovits and T. Kren{\'a}cs and Z. Tulassay and B. Moln{\'a}r",
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T1 - Intravenous Administration of a Single-Dose Free-Circulating DNA of Colitic Origin Improves Severe Murine DSS-Colitis

AU - Sípos, F.

AU - Müzes, G.

AU - Fűri, István

AU - Spisák, S.

AU - Wichmann, Barnabás

AU - Germann, Tiana M.

AU - Constantinovits, Miklós

AU - Krenács, T.

AU - Tulassay, Z.

AU - Molnár, B.

PY - 2014

Y1 - 2014

N2 - In inflammatory bowel diseases the presence of free-circulating DNA (fcDNA) sequences in the sera is an established phenomenon, albeit its real biological function still remains unclear. In our study the immunobiologic effects of a single-dose, intravenously administered fcDNA of normal and colitic origin were assayed in DSS-colitic and control mice. In parallel with disease and histological activity evaluations changes of the TLR9 and inflammatory cytokine signaling gene expression profiles were assayed in isolated cells of the lamina propria. Intravenously administered colitis-derived fcDNA displayed a more prominent beneficial action regarding the clinical and histological severity of DSS-colitis than that of fcDNA of normal origin. Systemic administration of colitis-derived fcDNA significantly altered the expression of certain TLR9-related and proinflammatory cytokine genes in a clinically favorable manner. Presumably due to induction of severe colitis, the subsequent marked inflammatory environment may result changes in fcDNA with a potential to promote the downregulation of inflammation and improvement of tissue regeneration. Elucidating mechanisms of innate immune alterations by nucleic acids may provide further insight into the etiology of inflammatory bowel diseases, and develop the basis of novel nucleic acid-based immunotherapies.

AB - In inflammatory bowel diseases the presence of free-circulating DNA (fcDNA) sequences in the sera is an established phenomenon, albeit its real biological function still remains unclear. In our study the immunobiologic effects of a single-dose, intravenously administered fcDNA of normal and colitic origin were assayed in DSS-colitic and control mice. In parallel with disease and histological activity evaluations changes of the TLR9 and inflammatory cytokine signaling gene expression profiles were assayed in isolated cells of the lamina propria. Intravenously administered colitis-derived fcDNA displayed a more prominent beneficial action regarding the clinical and histological severity of DSS-colitis than that of fcDNA of normal origin. Systemic administration of colitis-derived fcDNA significantly altered the expression of certain TLR9-related and proinflammatory cytokine genes in a clinically favorable manner. Presumably due to induction of severe colitis, the subsequent marked inflammatory environment may result changes in fcDNA with a potential to promote the downregulation of inflammation and improvement of tissue regeneration. Elucidating mechanisms of innate immune alterations by nucleic acids may provide further insight into the etiology of inflammatory bowel diseases, and develop the basis of novel nucleic acid-based immunotherapies.

KW - DSS-colitis

KW - Free-circulating DNA

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KW - Tissue regeneration

KW - Toll-like receptor 9

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