Beyond Proteostasis: the HSF1-Hsp Axis in Inflammation.

Inflammation is a multifaceted response involving molecular and cellular components triggered by diverse stimuli, including physical, chemical, and biological factors. The connection between these stimuli and inflammatory cellular responses involves numerous interactions among molecular components, resulting in cell outputs that can either help resolve potential harmful outcomes or amplify them, leading to further complications. Notably, heat shock factor 1 (HSF1), a transcription factor primarily associated with cellular responses to elevated temperatures, has also been reported to play a key role in modulating inflammation. Indeed, growing evidence suggests a close relationship between HSF1 and intracellular signaling pathways that regulate the secretion of inflammatory cytokines, impacting both infectious and non-infectious diseases. Furthermore, chaperone proteins known as heat shock proteins (Hsps), which HSF1 transcriptionally regulates, also play important roles during inflammation by modulating numerous host factors involved in this process. Here, we examine the interplay between HSF1 and Hsps in the context of inflammation caused by infectious and non-infectious diseases. We also discuss the potential benefits of targeting these factors as strategies for reducing the effects of exacerbated or damaging inflammation.