In situ correlation of cytokine secretion and apoptosis in Helicobacter pylori-associated gastritis.
Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important for the pathogenesis of Helicobacter pylori-associated gastritis and peptic ulcer disease. Gastric biopsies from H. pylori-positive and -negative patients were used to examine the in situ correlation of TNF-alpha and IFN-gamma with epithelial cell apoptosis, bacterial load, and histological parameters of gastritis. From the same patients, we isolated H. pylori-specific T cell lines and clones and examined their ex vivo release of proinflammatory cytokines. We found a highly significant correlation of TNF-alpha and IFN-gamma production with activity and grade of gastritis (P < 0.01), H. pylori density (P = 0.01), epithelial cell apoptosis (P < 0.001), and Fas/Fas-ligand expression (P < 0.001). T cell lines and clones were all TCR-alphabeta(+) and showed T helper 1 functional phenotype. With the use of serial histological sections, this study showed for the first time the in situ correlation of TNF-alpha and IFN-gamma with epithelial cell apoptosis, bacterial load, and histological severity of disease and emphasizes the role of these cytokines in the pathophysiology of H. pylori-associated disease.
Department of Gastroenterology, University Hospital of Basel, Switzerland.
Frank Serge
FS
Lehmann
Luigi
L
Terracciano
Ilaria
I
Carena
Christian
C
Baeriswyl
Jürgen
J
Drewe
Luigi
L
Tornillo
Gennaro
G
De Libero
Christoph
C
Beglinger
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002460:Cell Line; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism*; D053222:Fas Ligand Protein; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D006684:HLA-DR Antigens / Q000378:metabolism; D016481:Helicobacter Infections; D016480:Helicobacter pylori; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D013270:Stomach / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007371:Interferon-gamma