Inflammatory bowel disease (IBD), typified by ulcerative colitis and Crohn's disease, has an aetiology that appears to possess both genetic and environmental components. A number of mouse models of intestinal inflammation have been identified. For example, the interleukin (IL)-10 knockout mouse develops inflammation that is histologically similar to Crohn's disease1 while the IL-2 and T cell receptor α knockout animals develop inflammation that resembles ulcerative colitis.2 ,3 Together with other genetic mutant mouse models that develop IBD, these reports strongly support the view that genetic defects can predispose an individual to IBD. To our knowledge, however, the genetic defect models that have been described to date do not develop overt IBD if they are kept in a pathogen free environment, implying that the mucosal microflora plays a role in the initiation and/or perpetuation of the disease process. Despite the uncertain aetiology of IBD, the symptoms of the disease are associated with overproduction of proinflammatory cytokines and a commonly held view is that the disease is primarily a consequence of a deregulated adaptive immune system.

Transcriptional control of many inflammatory cytokines (including IL-4, tumour necrosis factor α (TNF-α), etc) is mediated by the transcription factor NF-κB,4 a key component in the inducible transcription of proinflammatory cytokines. NF-κB is normally retained in the cytoplasm by binding to its inhibitor protein, IκB, which masks the NF-κB nuclear localisation signal (NLS).5 A broad range of external stimuli that lead to activation of NF-κB set off signalling cascades that ultimately converge on the IκB kinase (IKK) complex.6 Activated IKK specifically and directly phosphorylates IκB and this phosphorylation event targets IκB for degradation.5 As a consequence, NF-κB NLS is uncovered and nuclear translocation occurs. External stimuli that can activate NF-κB include IL-1β, TNF-α, and bacterial lipopolysaccharide (LPS), the major …