Vol. 283, Issue 3, G511-G520, September 2002
TRANSLATIONAL PHYSIOLOGY
NSAIDs counteract H. pylori VacA toxin-induced
cell vacuolation in MKN 28 gastric mucosal cells
Vittorio
Ricci1,
Barbara A.
Manzo2,
Concetta
Tuccillo2,
Patrice
Boquet3,
Ulderico
Ventura1,
Marco
Romano2, and
Raffaele
Zarrilli4
1 Institute of Human Physiology, University of
Pavia, 27100 Pavia; 2 Department of Internal
Medicine, Chair of Gastroenterology, Second University of Naples
and 4 Department of Cellular and Molecular Biology
and Pathology "L. Califano," Institute of Experimental
Endocrinology and Oncology "G. Salvatore" of Consiglio Nazionale
delle Ricerche, Federico II University, 80131 Naples, Italy; and
3 Institut National de la Santé et de la
Recherche Médicale Unité 452, Nice University School of
Medicine, 06107 Nice Cedex 2, France
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.
aspirin; chloride channel blockers; cyclooxygenases; indomethacin; NS-398
