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, PGE(2), LTD(4), and 15-HETE on HSF-1-dependent gene expression in A549 human respiratory epithelial-like cells. When added at 1microM, PGE(2) much more than LTD(4), but not 15-HETE increased activity of a synthetic HSF-1-dependent reporter after HS exposure (42 degrees C for 2h), but had no effect in the absence of HS. Exposing A549 cells to HS stimulated the release of PGE(2) and treatment with the cyclooxygenase inhibitor, ibuprofen, reduced HS-induced HSF-1-dependent transcription. PGE(2) 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 PGE(2), which augments the generation of HSPs. The clinical consequences of this pathway have yet to be determined.
Shah
Nirav G
NG
Division of Pulmonary and Critical Care, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Tulapurkar
Mohan E
ME
Singh
Ishwar S
IS
Shelhamer
James H
JH
Cowan
Mark J
MJ
Hasday
Jeffrey D
JD
D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D010940:Plant Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D015232:Dinoprostone
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