EFFECTS OF STEROID TREATMENT ON ACTIVATION OF NUCLEAR FACTOR KAPPA-B IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE

Nuclear factor kappa B (NF kappa B) is a transcription factor that con trols several genes important for immunity and inflammation. The aim o f this study was to assess if activation of NF kappa B plays a role in the pathogenesis of inflammatory bowel disease (IBD), and whether ste roid treatment affects NF kappa B activation. Activation of NF kappa B was analysed in colon biopsy samples of 13 patients with active IBD ( 8 Crohn's colitis, 5 ulcerative colitis) by electrophoretic mobility-s hift assays, under basal conditions and 3 weeks after treatment with 0 .75 mg kg(-1) day(-1) prednisolone. The presence of interleukin-8 mRNA in biopsies was assessed by RT-PCR. A specific NF kappa B band was pr esent in all nuclear extracts from inflamed mucosa, whereas the band w as barely detectable in uninflamed colonic mucosa. NF kappa B bands we re super-shifted by antibodies against p50 subunit, whereas antibodies against p65, p52, c-Rel, or Rel B did not modify the mobility of the band. Increased interleukin-8 mRNA was detected at the same sites of N F kappa B activation. Steroid-induced healing of colonic inflammation was associated with disappearance of NF kappa B from nuclear extracts. These results support the notion that NF kappa B plays an important r ole in the pathogenesis of IBD, and that blockade of NF kappa B activa tion is one of the mechanisms by which steroids suppress the inflammat ory cascade in IBD.