Prostaglandin E2 potentiates heat shock-induced heat shock protein 72 expression in A549 cells

The heat shock (HS) response is an important cytoprotective response comprising the expression of heat shock proteins (HSPs) and orchestrated by the heat/stress-induced transcription factor, heat shock factor-1 (HSF-1). Previous studies suggest that the activation threshold and magnitude of the HS response may be modified by treatment with arachidonic acid (AA). We analyzed the effect of exogenous AA and its metabolites, PGE2, LTD4, and 15-HETE on HSF-1-dependent gene expression in A549 human respiratory epithelial-like cells. When added at 1 μM, PGE2 much more than LTD4, but not 15-HETE increased activity of a synthetic HSF-1-dependent reporter after HS exposure (42 °C for 2 h), but had no effect in the absence of HS. Exposing A549 cells to HS stimulated the release of PGE2 and treatment with the cyclooxygenase inhibitor, ibuprofen, reduced HS-induced HSF-1-dependent transcription. PGE2 increased HS-induced HSP72 mRNA and protein expression but EMSA and Western blot analysis failed to show an effect on HSF-1 DNA binding activity or post-translational modification. In summary, we showed that HS stimulates the generation of PGE2, which augments the generation of HSPs. The clinical consequences of this pathway have yet to be determined.