ARACHIDONATE IS A POTENT MODULATOR OF HUMAN HEAT-SHOCK GENE-TRANSCRIPTION

DA JURIVICH, Lea Sistonen, KD SARGE, RI MORIMOTO

    Research output: Contribution to journalArticleScientificpeer-review

    167 Citations (Scopus)

    Abstract

    Cell and tissue injury activate the inflammatory response through the action(s) of arachidonic acid and its metabolites, leading to the expression of acute-phase proteins and inflammatory cytokines. At the molecular level, little is known how arachidonic acid regulates the inflammatory response. As inflammation is also associated with local increase in tissue temperatures, we examined whether arachidonic acid was directly involved in the heat shock response. Extracellular exposure to arachidonic acid induced heat shock gene transcription in a dose-dependent manner via acquisition of DNA-binding activity and phosphorylation of heat shock factor 1 (HSF1). In addition, exposure of cells to low concentrations of arachidonic acid, which by themselves did not induce HSF1 DNA-binding activity, reduced the temperature threshold for HSF1 activation from elevated temperatures which are not physiologically relevant (>42 degrees C) to temperatures which can be attained during the febrile response (39-40 degrees C). These results indicate that elevated heat shock gene expression is a direct consequence of an arachidonic acid-mediated cellular response.
    Original languageUndefined/Unknown
    Pages (from-to)2280–2284
    Number of pages5
    JournalProceedings of the National Academy of Sciences
    Volume91
    Issue number6
    Publication statusPublished - 1994
    MoE publication typeA1 Journal article-refereed

    Keywords

    • HEAT SHOCK TRANSCRIPTION FACTORS
    • INFLAMMATION
    • PHOSPHORYLATION

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