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  • Title: The heat shock response inhibits inducible nitric oxide synthase gene expression by blocking I kappa-B degradation and NF-kappa B nuclear translocation.
    Author: Wong HR, Ryan M, Wispé JR.
    Journal: Biochem Biophys Res Commun; 1997 Feb 13; 231(2):257-63. PubMed ID: 9070260.
    Abstract:
    We investigated the mechanisms by which the heat shock response inhibits inducible nitric oxide synthase (iNOS) gene expression. Incubation of cultured murine lung epithelium (MLE-15) at temperatures ranging from 39 to 43 degrees C, for 1 h, demonstrated that only severe thermal stress (41 to 43 degrees C) was sufficient to induce the heat shock response. Thermal stress inhibited cytokine-mediated iNOS gene expression only when associated with induction of the heat shock response. Transient transfection assays with an iNOS promoter-reporter gene construct demonstrated that the heat shock response inhibited cytokine-mediated iNOS promoter activity. Electromobility gel shift assays demonstrated that the heat shock response inhibited cytokine-mediated NF-kappa B nuclear translocation. The heat shock response also inhibited cytokine-mediated I kappa-B degradation. These data suggest that the heat shock response inhibits iNOS gene expression by transcriptional mechanisms involving the NF-kappa B/ I kappa-B pathway.
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