Gastroduodenal mucosal defense.

PURPOSE OF REVIEW: We have summarized recent findings related to gastroduodenal mucosal defense as well as factors contributing to defensive failure, highlighting findings that illuminate new pathophysiological mechanisms.

RECENT FINDINGS: Gastroduodenal bicarbonate secretion is mediated by prostaglandin E receptors and stimulated by the prostone lubiprostone. Toll-like receptor (TLR)4 signaling is protective against gastric injury. Intestinal alkaline phosphatase (IAP) is a chemosensor that regulates the duodenal mucosal surface pH. Lipopolysaccharide (LPS) increases gastric permeability; IAP secreted during fat digestion may detoxify colonic LPS. NADPH oxidase activity mediates ischemia/reperfusion-related gastric mucosal damage. Heat shock protein 70 (HSP70) protects the gastric mucosa through inhibition of apoptosis, proinflammatory cytokines, and cell adhesion molecules (CAMs). HSP90 may be a contributing factor in impaired adaptive cytoprotection. Proteinase-activated receptor-1 (PAR-1) is protective against Helicobacter-induced gastritis, mediated by the suppression of proinflammatory pathways. IKK β/NF-κB signaling decreases chronic Helicobacter-induced inflammation by inhibiting cellular apoptosis and necrosis. Activation of A2A adenosine receptors decreases inflammation and gastritis but leads to persistent Helicobacter pylori infection.

SUMMARY: Enhanced understanding of the mechanisms of gastroduodenal defense and injury provides new insight into potential therapeutic targets, contributing towards the development of better tolerated and more effective therapies.