Cutting Edge: Typhlocolitis in NF-κB-Deficient Mice

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Abstract
Activation of inflammatory gene expression by the transcription factor NF-κB is a central pathway in many inflammatory disorders, including colitis. Increased NF-κB activity has been linked with development of colitis in humans and animal models, thus it was unexpected when NF-κB-deficient mice developed spontaneous typhlocolitis. To further characterize this finding, we induced typhlocolitis in rederived NF-κB-deficient mice using intragastric infection with Helicobacter hepaticus. At 6 wk postinfection (PI), severe colitis with increased type 1 cytokine expression was seen in infected mice that lacked the p50 subunit of NF-κB and were also heterozygous for the p65 subunit of NF-κB(p50−/−p65+/−). Mice lacking the p50 subunit alone (p50−/−) were less severely affected, and wild-type mice and p65+/− mice were unaffected. T cell development in NF-κB-deficient mice was normal. These data indicate that p50 and p65 subunits of NF-κB have an unexpected role in inhibiting the development of colitis.