Implication of NF-kappaB in Helicobacter pylori-associated gastritis.
OBJECTIVE
Transcription factor NF-kappaB plays a pivotal role in inflammatory responses by up-regulating mRNA expression of bioactive molecules such as chemokines and adhesion molecules. The present study was designed to elucidate the implication of NF-kappaB in Helicobacter pylori-associated gastritis (HAG).


METHODS
We examined 41 patients with HAG and 18 H. pylori-negative control subjects. Expression of activated NF-kappaB was studied in situ by immunohistochemistry using alpha-p65 mouse monoclonal antibody (alpha-p65 mAb), which recognizes activated NF-kappaB. To identify the cell types in which NF-kappaB was activated, we performed immunohistochemical analysis using antibodies against vascular endothelial cells, macrophages, and B and T lymphocytes. We also examined the colocalization of activated NF-kappaB with the of intercellular expression adhesion molecule-1 (ICAM-1) on endothelial cells. We measured the levels of NF-kappaB-dependent chemokines including interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage inflammatory protein-1alpha (MIP-1alpha) in antral mucosa by ELISA (ELISA).


RESULTS
Activated NF-kappaB was detected in the nuclei of epithelial cells in antral mucosa, especially of patients with HAG. NF-kappaB positivity index (NF-kappaB PI), representing the percentages of epithelial cells with positive nuclear staining for activated NF-kappaB, was significantly higher in patients with HAG than in H. pylori-negative controls. NF-kappaB PI correlated significantly with histological scores of gastritis. Moreover, activated NF-kappaB was identified in the nuclei of vascular endothelial cells, macrophages, and B lymphocytes within the lamina propria in HAG. Colocalization of activated NF-kappaB with ICAM-1 expression in the same endothelial cells was demonstrated. The IL-8 levels significantly correlated with the NF-kappaB PI.


CONCLUSIONS
In addition to epithelial cells, macrophages, vascular endothelial cells, and B lymphocytes contained activated NF-kappaB. In these cells, activated NF-kappaB may be involved in the inflammation process in HAG through the up-regulation of chemokines or adhesion molecules.
Isomoto
H
H
The Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Mizuta
Y
Y
Miyazaki
M
M
Takeshima
F
F
Omagari
K
K
Murase
K
K
Nishiyama
T
T
Inoue
K
K
Murata
I
I
Kohno
S
S
D000328:Adult; D000368:Aged; D000818:Animals; D018925:Chemokines / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000276:immunology* / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B