Gastric mucosal cell death induced by non-steroidal anti-inflammatory drugs (NSAIDs) is suggested to be involved in NSAID-induced gastric lesions. Therefore, cellular factors that suppress this cell death are important for protection of the gastric mucosa from NSAIDs. When cells are exposed to various stressors, including NSAIDs, they induce a number of proteins, so-called stress proteins, in order to protect themselves against such stressors. Stress proteins contain cytosolic molecular chaperons (such as heat shock proteins), endoplasmic reticulum molecular chaperons (such as glucose-regulated proteins) and heme oxygenase-1. We recently showed that (i) these stress proteins are up-regulated by NSAIDs both in vitro and in vivo; (ii) these up-regulation make gastric mucosal cells resistant to NSAIDs in vitro; (iii) these up-regulation protects the gastric mucosa from NSAID-induced gastric lesions in vivo. In this review, I summarize these results and propose that non-toxic inducers of these stress proteins are therapeutically beneficial as anti-ulcer drugs.
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