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

Fajun Yang, Willem J.S. De Villiers, Eun Y. Lee, Craig J. McClain, Gary W. Varilek

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Recent studies support nuclear factor-kappaB (NF-κB) as a critical transcription factor in inflammatory bowel disease. We examined NF-κB and its inhibitors, IκB-α and IκB-β, 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-κB and mRNA for NF-κB responsive cytokines interleukin-1β and tumor necrosis factor-alpha were markedly increased in interleukin-2(-/-) mice. Colon interleukin-1β protein levels were significantly elevated, consistent with increased interleukin-1β 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-κB responsive IκB-α was also increased, mirroring NF-κB activation. In contrast, IκB-β 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-κB-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-κB in the pathogenesis of intestinal inflammation in interleukin-2(-/-) mice. The measurement of NF-κB 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.

Original languageEnglish (US)
Pages (from-to)378-385
Number of pages8
JournalJournal of Laboratory and Clinical Medicine
Volume134
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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