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

Nat Med. 1996 Sep;2(9):998-1004. doi: 10.1038/nm0996-998.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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