title: TNF-alpha induces apoptosis of parietal cells.
abstract: 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.
authors.affiliation: Second Department of Medicine, Technical University of Munich, Ismaningerstr. 22, D-81675, Munich, Germany. bruno.neu@lrz.tum.de
authors.forename: Bruno
authors.initials: B
authors.lastname: Neu
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Puschmann
authors.forename: Artur
authors.initials: A
authors.lastname: Mayerhofer
authors.forename: Peter
authors.initials: P
authors.lastname: Hutzler
authors.forename: Johannes
authors.initials: J
authors.lastname: Grossmann
authors.forename: Florian
authors.initials: F
authors.lastname: Lippl
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schepp
authors.forename: Christian
authors.initials: C
authors.lastname: Prinz
mesh_terms: 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*
chemical_list: 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