Heat shock response during the resolution of inflammation and its progressive suppression in chronic-degenerative inflammatory diseases

Cell Stress Chaperones. 2024 Jan 18:S1355-8145(24)00042-7. doi: 10.1016/j.cstres.2024.01.002. Online ahead of print.ABSTRACTThe heat shock response (HSR) is a crucial biochemical pathway that orchestrates the resolution of inflammation, primarily under proteotoxic stress conditions. This process hinges on the upregulation of heat shock proteins (HSPs) and other chaperones, notably the 70kDa family of HSPs (HSP70s), under the command of the heat shock transcription factor-1 (HSF1). However, in the context of chronic degenerative disorders characterized by persistent low-grade inflammation - such as insulin resistance, obesity, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases - a gradual suppression of the HSR does occur. This work delves into the mechanisms behind this phenomenon. It explores how the Western diet and sedentary lifestyle, culminating in the endoplasmic reticulum (ER) stress within adipose tissue cells, trigger a cascade of events. This cascade includes the unfolded protein response (UPR) and activation of the NLRP3 inflammasome, leading to the emergence of the senescence-associated secretory phenotype (SASP) and the propagation of inflammation throughout the body. Notably, the activation of the NLRP3 inflammasome not only fuels inflammation but also sabotages the HSR by degrading HuR, a crucial mRNA-binding protein responsible for maintaining HSF1 mRNA expression and stability on heat shock gene promoters. This paper underscores th...
Source: Cell Stress and Chaperones - Category: Cytology Authors: Source Type: research