Effects of steroid treatment on activation of nuclear factor κB in patients with inflammatory bowel disease

Abstract

Nuclear factor κB (NFκB) is a transcription factor that controls several genes important for immunity and inflammation. The aim of this study was to assess if activation of NFκB plays a role in the pathogenesis of inflammatory bowel disease (IBD), and whether steroid treatment affects NFκB activation. Activation of NFκB was analysed in colon biopsy samples of 13 patients with active IBD (8 Crohn's colitis, 5 ulcerative colitis) by electrophoretic mobility-shift 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 NFκB band was present in all nuclear extracts from inflamed mucosa, whereas the band was barely detectable in uninflamed colonic mucosa. NFκB bands were 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 NFκB activation. Steroid-induced healing of colonic inflammation was associated with disappearance of NFκB from nuclear extracts. These results support the notion that NFκB plays an important role in the pathogenesis of IBD, and that blockade of NFκB activation is one of the mechanisms by which steroids suppress the inflammatory cascade in IBD.

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