Document Detail


Gastroduodenal mucosal defense.
MedLine Citation:
PMID:  20948371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Arushi deFoneska; Jonathan D Kaunitz
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review    
Journal Detail:
Title:  Current opinion in gastroenterology     Volume:  26     ISSN:  1531-7056     ISO Abbreviation:  Curr. Opin. Gastroenterol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-15     Completed Date:  2011-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8506887     Medline TA:  Curr Opin Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  604-10     Citation Subset:  IM    
Affiliation:
Greater Los Angeles Veteran Affairs Healthcare System, WLAVA Medical Center, Department of Medicine, UCLA School of Medicine, Los Angeles, California 90073, USA.
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MeSH Terms
Descriptor/Qualifier:
Alkaline Phosphatase / physiology
Amino Acids / physiology
Animals
Anti-Inflammatory Agents, Non-Steroidal / adverse effects
Bicarbonates / metabolism
Gastric Mucosa / drug effects,  metabolism*,  physiology
Heat-Shock Proteins / metabolism,  physiology
Helicobacter Infections / physiopathology
Helicobacter pylori
Humans
Hypoxia-Inducible Factor 1 / physiology
Intestinal Mucosa / metabolism*,  physiology
Oxidative Stress
Peptides / metabolism,  physiology
Phosphodiesterase Inhibitors / pharmacology
Prostaglandins / metabolism,  physiology
Reperfusion Injury / physiopathology
Toll-Like Receptors / metabolism
Grant Support
ID/Acronym/Agency:
P30 DK0413/DK/NIDDK NIH HHS; R01 DK54221/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Bicarbonates; 0/Heat-Shock Proteins; 0/Hypoxia-Inducible Factor 1; 0/Peptides; 0/Phosphodiesterase Inhibitors; 0/Prostaglandins; 0/Toll-Like Receptors; 146046-78-8/trefoil factor; EC 3.1.3.1/Alkaline Phosphatase

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