Cutting edge: Typhlocolitis in NF-kappa B-deficient mice

Activation of inflammatory gene expression by the transcription factor NF-k appaB is a central pathway in many inflammatory disorders, including coliti s. Increased NF-kappaB activity has been linked with development of colitis in humans and animal models, thus it was unexpected when NF-kappaB-deficie nt mice developed spontaneous typhlocolitis. To further characterize this f inding, we induced typhlocolitis in rederived NF-kappaB-deficient mice usin g 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-kappaB and were also heter ozygous for the p65 subunit of NF-kappaB(p50(-/-)p65(+/-)). Mice lacking th e p50 subunit alone (p50(-/-)) were less severely affected, and wild-type m ice and p65(+/-) mice were unaffected. T cell development in NF-kappaB-defi cient mice was normal. These data indicate that p50 and p65 subunits of NF- kappaB have an unexpected role in inhibiting the development of colitis.