Division of Pulmonary and Critical Care, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Prostaglandins Other Lipid Mediat. 2010 Sep;93(1-2):1-7. doi: 10.1016/j.prostaglandins.2010.03.006. Epub 2010 Apr 9.
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.
热休克 (HS) 反应是一种重要的细胞保护反应，包括热休克蛋白 (HSPs) 的表达，并由热/应激诱导转录因子热休克因子-1 (HSF-1) 协调。先前的研究表明，HS 反应的激活阈值和幅度可能通过用花生四烯酸 (AA) 处理来改变。我们分析了外源性 AA 及其代谢物 PGE(2)、LTD(4)和 15-HETE 对 A549 人呼吸道上皮样细胞中 HSF-1 依赖性基因表达的影响。当添加 1μM 时，PGE(2)比 LTD(4)更能增加 HS 暴露后（42°C 2 小时）合成 HSF-1 依赖性报告基因的活性，但在没有 HS 的情况下没有影响。使 A549 细胞暴露于 HS 会刺激 PGE(2)的释放，用环氧化酶抑制剂布洛芬处理会降低 HS 诱导的 HSF-1 依赖性转录。PGE(2)增加了 HS 诱导的 HSP72 mRNA 和蛋白表达，但 EMSA 和 Western blot 分析未能显示对 HSF-1 DNA 结合活性或翻译后修饰的影响。总之，我们表明 HS 刺激 PGE(2)的产生，从而增强 HSPs 的产生。该途径的临床后果尚未确定。
