Expression and activation of NF-kappa B in the antrum of the human stomach.
Both in vitro studies and experiments in mice suggest a key role for transcription factor NF-kappa B as a mediator of mucosal inflammation. Experiments in vitro show that NF-kappa B activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. This study examines the expression and activity of NF-kappa B in situ in antral biopsies of 69 consecutive patients with immunohistochemical techniques. In the uninflamed stomach, NF-kappa B was highly expressed and active in a subset of epithelial cells, which were identified as predominantly G cells. In accordance with this activity, G cells were shown to express high levels of the NF-kappa B target cytokine TNF-alpha, a well-documented stimulator of gastrin production. In patients with H. pylori-associated gastritis, NF-kappa B activity was markedly enhanced. Activation occurred preferentially in the epithelial cells. The number of cells showing activated NF-kappa B correlated with the activity of gastritis, a measure of neutrophil influx, whereas no correlation was found with the chronicity of inflammation, a measure of the presence of mononuclear inflammatory cells. This correlation is direct evidence of the importance of NF-kappa B-dependent signal transduction for neutrophil influx in H. pylori-associated gastritis.
van Den Brink
G R
GR
Departments of Experimental Internal Medicine, Pathology, and Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands. g.r.vandenbrink@amc.uva.nl
ten Kate
F J
FJ
Ponsioen
C Y
CY
Rive
M M
MM
Tytgat
G N
GN
van Deventer
S J
SJ
Peppelenbosch
M P
MP
D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D019863:Gastrin-Secreting Cells / Q000378:metabolism; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis* / Q000378:metabolism*; D011446:Prospective Studies; D011706:Pyloric Antrum / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha