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J Lab Clin Med. 1999 Oct;134(4):378-85.

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

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1
Department of Internal Medicine, University of Kentucky, Lexington, USA.

Abstract

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.

PMID:
10521084
[Indexed for MEDLINE]

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