The heat shock response (HSR) provides protection against stress-induced damage, and also prevents initiation of inflammatory gene expression via inhibition of NFκB activation. This article describes experiments demonstrating that the HSR prevents induction of nitric oxide synthase type 2 (NOS2) in rat brain. Twenty four hours after intrastriatal injection of lipopolysaccharide (LPS), IL-1β, and IFN-γ, NOS2 immunoreactive cells were detected in striatum, corpus callosum, and to a lesser extent in cortex. Induction of a HSR by whole body warming to 41°C for 20 minutes, done 1 day before LPS plus cytokine injection, reduced the number of NOS2-positive staining cells to background levels. Staining for ED1 antigen revealed that the HSR also suppressed microglial/brain macrophage activation in the same areas. Striatal injection of LPS and cytokines induced the rapid activation of NFκB, and this activation was prevented by prior HS, which also increased brain IκB-α expression. These results suggest that establishment of a HSR can reduce inflammatory gene expression in brain, mediated by inhibition of NFκB activation, and may therefore offer a novel approach to treatment and prevention of neurological disease and trauma.
Nitric oxide-heat shock protein axis in menopausal hot flushes: neglected metabolic issues of chronic inflammatory diseases associated with deranged heat shock response