Apoptosis induction in gastric mucous cells in vitro: lesser potency of Helicobacter pylori than Escherichia coli lipopolysaccharide, but positive interaction with ibuprofen.
Non-steroidal anti-inflammatory drugs (NSAIDs) cause peptic ulcer disease, but whether they interact with Helicobacter pylori to promote damage is controversial. Moreover, the reported induction of apoptosis in gastric cells by H. pylori lipopolysaccharide (LPS) (10(-9) g/ml) contrasts with studies showing low immunological potency of this LPS. Therefore, the effects of LPS from H. pylori NCTC 11637 and Escherichia coli O111:B4 on apoptosis in a primary culture of guinea-pig gastric mucous cells were investigated in the presence and absence of the NSAID, ibuprofen. Cell loss was estimated by a crystal violet assay, and apoptosis determined from caspase activity and from condensation and fragmentation of nuclei. Exposure to E. coli LPS for 24 h caused cell loss and enhanced apoptotic activity at concentrations >or= 10(-9) g/ml, but similar effects were only obtained with H. pylori LPS at concentrations >or= 10(-6) g/ml. Although ibuprofen (250 microM) caused cell loss and apoptosis, addition of either E. coli or H. pylori LPSs further enhanced these effects. In conclusion, LPS and ibuprofen interact to enhance gastric cell loss and apoptosis. In such interactions, E. coli LPS is more potent than that of H. pylori. The low potency of H. pylori LPS may contribute to a chronic low-grade gastritis that can be enhanced by the use of NSAIDs.
Durkin
Emma
E
School of Life and Health Sciences, Aston University, Birmingham, UK.
Moran
Anthony P
AP
Hanson
Peter J
PJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects; D004926:Escherichia coli / Q000737:chemistry*; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects; D005840:Gentian Violet; D006168:Guinea Pigs; D016480:Helicobacter pylori / Q000737:chemistry*; D007052:Ibuprofen / Q000633:toxicity*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D013936:Thymidine / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004396:Coloring Agents; D008070:Lipopolysaccharides; D004247:DNA; D020169:Caspases; D005840:Gentian Violet; D006690:Bisbenzimidazole; D013936:Thymidine; D007052:Ibuprofen