ACTIVATION OF NUCLEAR FACTOR KAPPA-B IN INFLAMMATORY BOWEL-DISEASE

Background-Expression of pro-inflammatory cytokines is increased in th e intestinal lamina propria of patients with inflammatory bowel diseas e (IBD). Nuclear factor kappa B (NF kappa B) controls transcription of inflammation genes. On activation, NF kappa B is rapidly released fro m its cytoplasmic inhibitor (I kappa B), transmigrates into the nucleu s, and binds to DNA response elements in gene promoter regions. Aims-T o investigate whether increased activation of NF kappa B is important in IBD and may be down-regulated by antiinflammatory treatment. Method s-Activation of NF kappa B was determined by western blot assessment a nd electrophoretic mobility shift assay in nuclear extracts of colonic biopsy samples as well as lamina propria mononuclear cells. Results-N uclear levels of NF kappa B p65 are increased in lamina propria biopsy specimens from patients with Crohn's disease in comparison with patie nts with ulcerative colitis and controls. Increased activation of NF k appa B was detected in lamina propria mononuclear cells from patients with active IBD. Corticosteroids strongly inhibit intestinal NF kappa B activation in IBD in vivo and in vitro by stabilising the cytosolic inhibitor I kappa B alpha against activation induced degradation. Conc lusions-In both IBDs, but particularly Crohn's disease, increased acti vation of NF kappa B may be involved in the regulation of the inflamma tory response. Inhibition of NF kappa B activation may represent a mec hanism by which steroids exert an anti-inflammatory effect in IBD.