Effects of steroid treatment on activation of nuclear factor kappaB in patients with inflammatory bowel disease.
Nuclear factor kappB (NFkappaB) is a transcription factor that controls several genes important for immunity and inflammation. The aim of this study was to assess if activation of NFkappaB plays a role in the pathogenesis of inflammatory bowel disease (IBD), and whether steroid treatment affects NFkappaB activation. Activation of NFkappaB 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 NFkappaB band was present in all nuclear extracts from inflamed mucosa, whereas the band was barely detectable in uninflamed colonic mucosa. NFkappaB 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 NFkappaB activation. Steroid-induced healing of colonic inflammation was associated with disappearance of NFkappaB from nuclear extracts. These results support the notion that NFkappaB plays an important role in the pathogenesis of IBD, and that blockade of NFkappaB activation is one of the mechanisms by which steroids suppress the inflammatory cascade in IBD.
Ardite
E
E
Consejo Superior Investigaciones Científicas, Barcelona, Spain.
Panés
J
J
Miranda
M
M
Salas
A
A
Elizalde
J I
JI
Sans
M
M
Arce
Y
Y
Bordas
J M
JM
Fernández-Checa
J C
JC
Piqué
J M
JM
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D011239:Prednisolone