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Local administration of antisense phosphorothiate olignucleotides to the p65 subunit of NF–κB abrogates established experimental colitis in mice

Nature Medicine volume 2, pages 998–1004 (1996)Cite this article

Abstract

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–κB 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.

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Authors and Affiliations

  1. Laboratory of Immunology, I. Medical Clinic, University of Mainz, Langenbeckstrasse 1, 55101, Mainz, Germany

    Markus F. Neurath & Karl-Hermann Meyer Zum Büschenfelde

  2. Center of Biotechnology, Karolinska Institute, 14157, Huddinge, Sweden

    Sven Pettersson

  3. Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, 20892, USA

    Warren Strober

Authors
  1. Markus F. Neurath
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  2. Sven Pettersson
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  3. Karl-Hermann Meyer Zum Büschenfelde
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  4. Warren Strober
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Neurath, M., Pettersson, S., Meyer Zum Büschenfelde, KH. et al. Local administration of antisense phosphorothiate olignucleotides to the p65 subunit of NF–κB abrogates established experimental colitis in mice. Nat Med 2, 998–1004 (1996). https://doi.org/10.1038/nm0996-998

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