Increased nuclear factor-kappaB activation in colitis of interleukin-2-deficient mice

J Lab Clin Med. 1999 Oct;134(4):378-85. doi: 10.1016/s0022-2143(99)90152-x.


Recent studies support nuclear factor-kappaB (NF-kappaB) as a critical transcription factor in inflammatory bowel disease. We examined NF-kappaB and its inhibitors, IkappaB-alpha and IkappaB-beta, in the colitis of interleukin-2 deficient (IL-2-/-) mice at the ages of 5, 10, and 15 weeks and compared them with those of age-matched wild-type mice. Colon levels of nuclear NF-kappaB and mRNA for NF-kappaB responsive cytokines interleukin-1beta and tumor necrosis factor-alpha were markedly increased in interleukin-2-/-mice. Colon interleukin-1beta protein levels were significantly elevated, consistent with increased interleukin-1beta mRNA, whereas tumor necrosis factor-alpha protein levels were either lower than those of the control group or did not differ. Protein levels of the immunomodulatory cytokine interleukin-10 were diminished. The NF-kappaB responsive IkappaB-alpha was also increased, mirroring NF-kappaB activation. In contrast, IkappaB-beta levels did not differ from those of wild-type mice in the 5- and 10-week groups and were only mildly increased in the 15-week group. Serum amyloid A, an acute phase protein that also is NF-kappaB-responsive, was dramatically elevated in the serum of interleukin-2-/- mice and correlated with the severity of the colitis. These data support a role for NF-kappaB in the pathogenesis of intestinal inflammation in interleukin-2-/- mice. The measurement of NF-kappaB in colon tissue samples may provide a sensitive means of assessing the state of activation of the mucosal immune response, and serum amyloid A appears to be a reliable biochemical marker of disease activity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute-Phase Reaction / immunology
  • Animals
  • Biomarkers
  • Cell Nucleus / chemistry
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / pathology
  • Cytosol / chemistry
  • Female
  • Gene Expression / immunology
  • Genotype
  • I-kappa B Proteins / analysis
  • I-kappa B Proteins / metabolism
  • Interleukin-1 / analysis
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology
  • Interleukin-10 / analysis
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-2 / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • NF-kappa B / analysis
  • NF-kappa B / metabolism*
  • RNA, Messenger / analysis
  • Rectal Prolapse / immunology
  • Rectal Prolapse / metabolism
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology


  • Biomarkers
  • I-kappa B Proteins
  • Interleukin-1
  • Interleukin-2
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10