Increased nuclear factor-kappaB activation in colitis of interleukin-2-deficient mice.
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.
Yang
F
F
Department of Internal Medicine, University of Kentucky, Lexington, USA.
de Villiers
W J
WJ
Lee
E Y
EY
McClain
C J
CJ
Varilek
G W
GW
D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D015415:Biomarkers; D002467:Cell Nucleus / Q000737:chemistry; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003600:Cytosol / Q000737:chemistry; D005260:Female; D015870:Gene Expression / Q000276:immunology; D005838:Genotype; D020672:I-kappa B Proteins / Q000032:analysis / Q000378:metabolism; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012005:Rectal Prolapse / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000276:immunology
D015415:Biomarkers; D020672:I-kappa B Proteins; D007375:Interleukin-1; D007376:Interleukin-2; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10