Bacterial endotoxin modifies heat shock factor-1 activity in RAW 264.7 cells: implications for TNF-α regulation during exposure to febrile range temperatures

Recent studies have identified heat shock factor (HSF)-1, the predominant heat/stress-stimulated transcriptional activator of heat shock protein genes as a repressor of certain cytokine genes, including TNF-α and IL-1β. We previously showed that exposing macrophages to febrile-range temperature (FRT; 39.5°C) activates HSF-1 to a DNA binding form that does not activate heat shock protein gene transcription, but apparently represses TNF-α and IL-1β transcription. Prewarming macrophages to 39.5°C for 30 min prior to stimulation with bacterial lipopolysaccharide (LPS) does not change the induction of TNF-α transcription, but markedly reduces its duration. This raised the question of how TNF-α transcription could occur at all in the presence of activated HSF-1. We used RAW 264.7 cells to test the hypothesis that macrophage activation triggers a transient reversal of HSF-1-mediated repression, thereby allowing induction of TNF-α transcription. Electrophoretic mobility shift assays revealed that LPS triggers a t...