Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa.
OBJECTIVE
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.
Rogler
G
G
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
Brand
K
K
Vogl
D
D
Page
S
S
Hofmeister
R
R
Andus
T
T
Knuechel
R
R
Baeuerle
P A
PA
Schölmerich
J
J
Gross
V
V
D000328:Adult; D000368:Aged; D004591:Electrophoresis, Polyacrylamide Gel; D004751:Enteritis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology*; D012016:Reference Values
D016328:NF-kappa B