Gastroduodenal mucosal defense.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Greater Los Angeles Veteran Affairs Healthcare System, WLAVA Medical Center, Department of Medicine, UCLA School of Medicine, Los Angeles, California 90073, USA.
Arushi
A
deFoneska
Jonathan D
JD
Kaunitz
D000469:Alkaline Phosphatase / Q000502:physiology; D000596:Amino Acids / Q000502:physiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001639:Bicarbonates / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology; D016481:Helicobacter Infections / Q000503:physiopathology; D016480:Helicobacter pylori; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress; D010455:Peptides / Q000378:metabolism / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology; D051193:Toll-Like Receptors / Q000378:metabolism; D000071164:Trefoil Factor-2
D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D006360:Heat-Shock Proteins; D051793:Hypoxia-Inducible Factor 1; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins; D051193:Toll-Like Receptors; D000071164:Trefoil Factor-2; D000469:Alkaline Phosphatase