NSAIDs counteract H. pylori VacA toxin-induced cell vacuolation in MKN 28 gastric mucosal cells.
The relationship between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori-induced gastric mucosal injury is still under debate. VacA toxin is an important H. pylori virulence factor that causes cytoplasmic vacuolation in cultured cells. Whether and how NSAIDs affect VacA-induced cytotoxicity is unclear. This study was designed to evaluate the effect of NSAIDs on H. pylori VacA toxin-induced cell vacuolation in human gastric mucosal cells in culture (MKN 28 cell line). Our data show that 1) NSAIDs (indomethacin, aspirin, and NS-398) inhibit VacA-induced cell vacuolation independently of inhibition of cell proliferation and prostaglandin synthesis; 2) NSAIDs impair vacuole development/maintenance without affecting cell binding and internalization of VacA; and 3) NSAIDs, as well as the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid, also inhibit cell vacuolation induced by ammonia. We thus hypothesize that NSAIDs might protect MKN 28 cells against VacA-induced cytotoxicity by inhibiting VacA channel activity required for vacuole genesis.
Ricci
Vittorio
V
Institute of Human Physiology, University of Pavia, 27100 Pavia, Italy. ricci@chifis.unipv.it
Manzo
Barbara A
BA
Tuccillo
Concetta
C
Boquet
Patrice
P
Ventura
Ulderico
U
Romano
Marco
M
Zarrilli
Raffaele
R
D000641:Ammonia / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004167:Diphtheria Toxin / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D009579:Nitrobenzoates / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D012276:Ricin / Q000494:pharmacology; D014617:Vacuoles / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001426:Bacterial Proteins; D018118:Chloride Channels; D004167:Diphtheria Toxin; D009579:Nitrobenzoates; D011448:Prostaglandin Antagonists; C074689:VacA protein, Helicobacter pylori; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000641:Ammonia; D012276:Ricin