TNF-alpha induces apoptosis of parietal cells.
Helicobacter pylori infection can be associated with chronic gastric inflammation and hypochlorhydria with increased levels of the proinflammatory cytokines. The current study investigated the effects of TNF-alpha on programmed death of gastric parietal cells. TNF-alpha induced apoptosis of parietal cells in isolated perfused rat stomachs at 10ng/mL. In isolated and highly enriched rat parietal cells, 10ng/mL TNF-alpha induced a 2.6-fold increase in the apoptotic rate. The 55kDa protein of TNFR-1 but not the 75kDa of TNFR-2 was detected by Western blot analysis. TNF-alpha-induced apoptosis of isolated parietal cells was inhibited by pretreatment with different NF-kappaB-inhibitors, nitric oxide synthase inhibitors and with antisense-oligodeoxynucleotides against the p65 subunit of NF-kappaB. Investigation of downstream signaling pathways of apoptosis revealed that TNF-alpha induced the expression of iNOS, but failed to stimulate the activity of caspase 3. The TNF-alpha effect on gastric parietal cells may contribute to the atrophy and hypochlorhydria of the gastric mucosa observed during chronic H. pylori infection.
Neu
Bruno
B
Second Department of Medicine, Technical University of Munich, Ismaningerstr. 22, D-81675, Munich, Germany. bruno.neu@lrz.tum.de
Puschmann
Andreas J
AJ
Mayerhofer
Artur
A
Hutzler
Peter
P
Grossmann
Johannes
J
Lippl
Florian
F
Schepp
Wolfgang
W
Prinz
Christian
C
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases