NSAID-induced antral ulcers linked with gene expression changes
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Jun 29, 2009
MedWire News: Patients who develop antral ulcers after treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) may display distinct changes in mucosal gene expression, US research suggests.
The findings could offer an insight into the molecular basis of susceptibility to mucosal injury, say J Aisenberg (Mount Sinai Medical Center, New York) and colleagues.
The team chose to study 23 genes that encode proteins that are important in mucosal inflammation and repair. Changes in mucosal expression on biopsy following a week of NSAID treatment were compared in healthy volunteers who developed antral ulcers and those who did not.
The 18 individuals who developed antral ulcers had significantly greater mucosal up-regulation of interleukin (IL)-8 after treatment, with a mean 33.5-fold increase from baseline compared with a 7.7-fold decrease in the seven who did not develop ulcers.
The same was true for cyclo-oxygenase (COX)-2, with a mean 2.3-fold up-regulation in those with ulcers compared with a 10.8-fold decrease in those without ulcers.
In contrast, participants without ulcers had significantly greater up-regulation of toll-like receptor (TLR)-4 compared with a 14.0-fold increase compared with an 0.8-fold decrease in those who developed ulcers.
The same was true for COX-1, with a 9.8-fold increase versus no change, and this was also the case for hepatocyte growth factor (HGF), with an increase of 8.2 fold versus a decrease of 2.2 fold, respectively.
“Our results suggest that NSAID-induced antral ulcers are associated with a specific pattern of mucosal gene regulation,” the researchers report in the journal Alimentary Pharmacology and Therapeutics.
“Up-regulation of HGF-1, COX-1 and TLR-4 is associated with decreased NSAID injury, while up-regulation of IL-8 may represent a mechanism of injury,” they add.
“Detailed analysis of pathways involving HGF-1, COX-1, COX-2, TLR-4 and IL-8 using tissue obtained from endoscopic biopsy specimens may yield useful information regarding the mechanisms of NSAID-related injury.”
