Intravenous administration of a single-dose free-circulating DNA of colitic origin improves severe murine DSS-colitis.
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.
Cell Analysis Laboratory, 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi Street 46, 1088, Budapest, Hungary, dr.siposf@gmail.com.
Ferenc
F
Sipos
Györgyi
G
Műzes
István
I
Fűri
Sándor
S
Spisák
Barnabás
B
Wichmann
Tiana M
TM
Germann
Miklós
M
Constantinovits
Tibor
T
Krenács
Zsolt
Z
Tulassay
Béla
B
Molnár
D061605:Administration, Intravenous; D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D004247:DNA / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D004247:DNA; D016264:Dextran Sulfate