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

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-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.

• Authors: M F Neurath, S Pettersson, K H Meyer zum Büschenfelde, W Strober
• Journal: Nature medicine (Nat Med) Vol. 2 Issue 9 Pg. 998-1004 (Sep 1996) ISSN: 1078-8956 [Print] United States
• PMID: 8782457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Cytokines
• NF-kappa B
• Oligonucleotides, Antisense
• Transcription Factor RelA
• Interleukin-10
• Trinitrobenzenesulfonic Acid
• DNA

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Animals
• Base Sequence
• Cells, Cultured
• Crohn Disease (drug therapy, genetics, immunology)
• Cytokines (biosynthesis)
• DNA
• Disease Models, Animal
• Enterocolitis (drug therapy, immunology)
• Female
• Humans
• Interleukin-10 (deficiency)
• Male
• Mice
• Middle Aged
• Molecular Sequence Data
• NF-kappa B (antagonists & inhibitors, genetics, physiology)
• Oligonucleotides, Antisense (therapeutic use)
• Transcription Factor RelA
• Trinitrobenzenesulfonic Acid