Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa

Gastroenterology. 1998 Aug;115(2):357-69. doi: 10.1016/s0016-5085(98)70202-1.

Abstract

Background & aims: Transcription factors of the nuclear factor kappaB (NF-kappaB) family play an important role in the regulation of genes involved in inflammation. In inflammatory bowel diseases, proinflammatory cytokines known to be regulated by NF-kappaB are involved. The aim of this study was to investigate the role of NF-kappaB activation during mucosal inflammation in situ.

Methods: A monoclonal antibody, alpha-p65mAb, was applied for immunofluorescence and immunohistochemical analysis that recognizes activated NF-kappaB. Electrophoretic mobility shift assay was used to directly demonstrate the presence of active DNA-binding NF-kappaB.

Results: Using the alpha-p65mAb antibody, activated NF-kappaB could be found in biopsy specimens from inflamed mucosa but was almost absent in uninflamed mucosa. The number of cells showing NF-kappaB activation correlated with the degree of mucosal inflammation but was not significantly different between inflamed mucosa from patients with Crohn's disease, ulcerative colitis, and nonspecific colitis or diverticulitis. NF-kappaB activation was localized in macrophages and in epithelial cells as identified by double-labeling techniques. Electrophoretic mobility shift assay with isolated lamina propria mononuclear cells and epithelial cells confirmed these results.

Conclusions: This study shows for the first time the activation of NF-kappaB during human mucosal inflammation in situ. In addition to macrophages, epithelial cells contained activated NF-kappaB, indicating an involvement in the inflammatory process.

MeSH terms

  • Adult
  • Aged
  • Electrophoresis, Polyacrylamide Gel
  • Enteritis / metabolism*
  • Enteritis / pathology
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • NF-kappa B / physiology*
  • Reference Values

Substances

  • NF-kappa B