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Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice

Nature medicine. Bd. 2. H. 9. New York: Nature Publishing Group 1996 S. 998 - 1004

Erscheinungsjahr: 1996

ISBN/ISSN: 1078-8956 ; 1546-170X

Publikationstyp: Zeitschriftenaufsatz

Sprache: Englisch

Doi/URN: 10.1038/nm0996-998

Volltext über DOI/URN

Geprüft:Bibliothek

Inhaltszusammenfassung


Chronic intestinal inflammation induced by 2,4,6,-trinitrobenzene sulfonic acid (TNBS) is characterized by a transmural granulomatous colitis that mimics some characteristics of human Crohn's disease. Here, we show that the transcription factor NF-kappa B p65 was strongly activated in TNBS-induced colitis and in colitis of interleukin-10-deficient mice. Local administration of p65 antisense phosphorothioate oligonucleotides abrogated clinical and histological signs of colitis and was more eff...Chronic intestinal inflammation induced by 2,4,6,-trinitrobenzene sulfonic acid (TNBS) is characterized by a transmural granulomatous colitis that mimics some characteristics of human Crohn's disease. Here, we show that the transcription factor NF-kappa B p65 was strongly activated in TNBS-induced colitis and in colitis of interleukin-10-deficient mice. Local administration of p65 antisense phosphorothioate oligonucleotides abrogated clinical and histological signs of colitis and was more effective in treating TNBS-induced colitis than single or daily administration of glucocorticoids. The data provide direct evidence for the central importance of p65 in chronic intestinal inflammation and suggest a potential therapeutic utility of p65 antisense oligonucleotides as a novel molecular approach for the treatment of patients with Crohn's disease.» weiterlesen» einklappen

Autoren


Neurath, Markus F. (Autor)
Pettersson, Sven (Autor)
Meyer zum Büschenfelde, Karl-Hermann (Autor)
Strober, Warren (Autor)

Klassifikation


DDC Sachgruppe:
Medizin