Background and Aims: The cyclooxygenase (COX) enzymes catalyze the initial step of prostaglandin formation; the inducible form, COX-2, plays a role in inflammation. Heat-shock protein 70 (hsp70) is a stress-responsive gene important for cell survival; induction of hsp70 appears to be mediated, in part, by the prostaglandin pathway. We determined the effect of COX-2 overexpression on hsp70 induction in rat intestinal epithelial (RIE) cells. Methods: RIE cells transfected with COX-2 complementary DNA oriented in the sense (RIE-S) or antisense (RIE-AS) direction were subjected to a heat shock; RNA and protein were harvested and analyzed by Northern and Western blots, respectively. Gel shift assays were performed to assess DNA binding. Results: Both hsp70 messenger RNA and HSP70 protein levels were increased in the RIE- AS cells, whereas induction was markedly inhibited in the RIE-S cells after heat shock. Inhibition of heat-shock factor binding was noted in RIE-S cells, suggesting that heat-shock transcription factor regulation may explain the inhibition of hsp70. The COX-2 selective inhibitor, NS-398, reversed the effects of COX-2 overexpression. Conclusions: The results support a functional role for the prostaglandin/COX pathway in the induction of hsp70. The findings underscore a potential regulatory mechanism involving an inverse relationship between COX-2 expression and hsp70 induction.
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