Disruption in gastric mucin synthesis by Helicobacter pylori lipopolysaccharide involves ERK and p38 mitogen-activated protein kinase participation

Helicobacter pylori is a primary factor in the etiology of gastric disease, and its early pathogenic effects are manifested by up-regulation of inflammatory processes and the loss of mucus coat continuity. We investigated the role of extracellular signal-regulated kinase (ERK) and p38 mitogen activated protein kinase (MAPK) in the disturbances in gastric mucin synthesis and apoptotic processes evoked by H. pylori lipopolysaccharide (LPS). Exposure of gastric mucosal cells to the LPS led to a dose-dependent decrease (up to 59.5%) in mucin synthesis, accompanied by a marked increase in caspase-3 activity and apoptosis. Inhibition of ERK with PD98059 accelerated (up to 36.1%) the LPS-induced decrease in mucin synthesis, and caused further enhancement in caspase-3 activity and apoptosis. Blockade of p38 kinase with SB203580 produced reversal in the LPS-induced reduction in mucin synthesis, and substantially countered the LPS-induced increases in caspas-3 activity and apoptosis. Moreover, inhibition of caspase-3 blocked the LPS-induced increase in caspse-3 activity and produced an increase in mucin synthesis. Thus the detrimental influence of H. pylori LPS on gastric mucin synthesis is closely linked to caspase-3 activation and apoptosis, and involves ERK and p38 kinase participation.