Observations that nonsteroidal anti-inflammatory drugs (NSAIDs) cause mucosal injury in both the stomach and small intestine have stimulated the search for protective options. Recent observations have shown that the heat shock proteins (Hsp), and Hsp70 in particular, can protect tissues from a range of stressors, including NSAID injury. In this issue, Asano et al., examine the possible role of Hsp70 in protection against NSAID-induced lesions in the small intestine. The study found that indomethacin induces mucosal cell apoptosis and proinflammatory cytokines in the small intestine in vivo. The damage was significantly reduced in mice that constitutively express high levels of Hsp70. The injury was also significantly attenuated when the animals were given oral geranylgeranyl acetone (GGA) to induce Hsp70 expression. Results from this work demonstrate that increasing Hsp70 protects against mucosal apoptosis, inflammation, and cytokine production in indomethacin-induced injury and suggest that GGA could be used therapeutically to regulate Hsp70 expression and, hence, protection against lesion formation in patients who consume NSAIDs. It is interesting to note that GGA has already been in use in Japan for effective treatment of gastric ulcers.
See article at J Pharmacol Exp Ther 2009, 330:458-467.
- The American Society for Pharmacology and Experimental Therapeutics