Gastroduodenal mucosal defense.
OBJECTIVE
The gastroduodenum has multiple means by which it resists injury from intrinsic and extrinsic factors, including gastric acid, nonsteroidal anti-inflammatory drugs, and Helicobacter pylori. We review recent insights into the mechanisms by which the gastroduodenum resists injury and discuss factors contributing to defensive failure.


RESULTS
Duodenal bicarbonate secretion, a primary defensive mechanism, is mediated by the downregulated in adenoma anion exchanger and is stimulated by estrogens. Nonsteroidal anti-inflammatory drug gastric damage is dependent on toll-like receptor signaling. Portal hypertensive gastropathy impairs extracellular signal-regulated kinase 1/2 phosphorylation, increasing oxidative stress. H. pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses.


CONCLUSIONS
Enhanced understanding of the mechanisms of gastroduodenal defense and injury provides new insight into potential therapeutic targets, which contributes towards the development of more well tolerated and more effective therapies.
Nayeb-Hashemi
Hamed
H
aDepartment of Internal Medicine, UCLA Medical Center, USA bGreater Los Angeles Veteran Affairs Healthcare System, WLAVA Medical Center, Los Angeles, California, USA.
Kaunitz
Jonathan D
JD
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D001639:Bicarbonates / Q000378:metabolism*; D004386:Duodenum / Q000276:immunology* / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori; D006801:Humans; D006975:Hypertension, Portal / Q000276:immunology*; D018928:Immunity, Mucosal / Q000502:physiology*; D000070116:Lotus / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D009479:Neuropeptides / Q000502:physiology; D018384:Oxidative Stress; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000276:immunology; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D009077:Mucins; D009479:Neuropeptides; D042461:Vascular Endothelial Growth Factor A; D001241:Aspirin