NUCLEAR FACTOR KAPPA-B IS ACTIVATED IN MACROPHAGES AND EPITHELIAL-CELLS OF INFLAMED INTESTINAL-MUCOSA

Background & Aims: Transcription factors of the nuclear factor kappa B (NF-kappa B) family play an important role in the regulation of genes involved in inflammation. In inflammatory bowel diseases, proinflamma tory cytokines known to be regulated by NF-kappa B are involved. The a im of this study was to investigate the role of NF-kappa B activation during mucosal inflammation in situ. Methods: A monoclonal antibody, a lpha-p65mAb, was applied for immunofluorescence and immunohistochemica l analysis that recognizes activated NF-kappa B. Electrophoretic mobil ity shift assay was used to directly demonstrate the presence of activ e DNA-binding NF-kappa B. Results: Using the alpha-p65mAb antibody, ac tivated NF-kappa B could be found in biopsy specimens from inflamed mu cosa but was almost absent in uninflamed mucosa. The number of cells s howing NF-kappa B activation correlated with the degree of mucosal inf lammation but was not significantly different between inflamed mucosa from patients with Crohn's disease, ulcerative colitis, and nonspecifi c colitis or diverticulitis. NF-kappa B activation was localized in ma crophages and in epithelial cells as identified by double-labeling tec hniques. Electrophoretic mobility shift assay with isolated lamina pro pria mononuclear cells and epithelial cells confirmed these results. C onclusions: This study shows for the first time the activation of NF-k appa B during human mucosal inflammation in situ. In addition to macro phages, epithelial cells contained activated NF-kappa B, indicating an involvement in the inflammatory process.