Alimentary TractNuclear factor κB is activated in macrophages and epithelial cells of inflamed intestinal mucosa☆
Section snippets
Monoclonal antibody α-p65mAb
Production and characteristics of the monoclonal antibody α-p65mAb have been described in detail previously.30, 31, 32 The antibody was designed to bind to a region of the p65 subunit of NF-κB that is masked in the NF-κB–IκB complex. Only when IκB is released from the complex, binding of the α-p65mAb can occur. Therefore, it allows the exclusive identification of activated NF-κB (after IκB release) in situ. The antibody is suitable for immunohistochemical and immunofluorescence techniques
Patients
The cryostat sections used for the experiments were obtained from biopsy specimens of inflamed colon of 25 patients with ulcerative colitis, 23 patients with Crohn's disease, 4 patients with diverticulitis, 4 patients with nonspecific colitis, and 21 control patients. The control patients were older than the patients with inflammatory bowel disease (Table 1). None of the control patients was treated with corticosteroids, whereas 10 patients with Crohn's disease and 12 patients with ulcerative
Discussion
Recently Neurath et al. described an abrogation of experimental colitis in mice by local administration of p65 antisense oligonucleotides.11 They also examined the regulation of p65 in patients with Crohn's disease and found a significant up-regulation of p65 mRNA and protein levels in macrophages and endothelial cells from these patients compared with cells from normal mucosa. These studies were performed with isolated cells. Furthermore, the activation state of NF-κB was not addressed. In the
Acknowledgements
The authors thank E. Treher, W. Vogt, and S. Gruene for supplying biopsy samples.
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Address requests for reprints to: Gerhard Rogler, M.D., Ph.D., Department of Internal Medicine I, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany. Fax: (49) 941-944-7002.