The inflammation is a key process in the general physiology of an organism, and one of the first to be involved in the immune response. Its activity is mediated by molecular platforms called inflammasomes. The NLRP3 inflammasome is the most studied and is involved in the maturation of caspase-1, a protease responsible for the secretion of Il-1β and Il-18. Its regulation is tightly controlled via a wide variety of phenomenon and is a vital process to maintain the correct physiology of an organism.
The goal of our study is to determine the effects of the protein HSP70 on the NLRP3 inflammasome. We have shown in human Thp1 cells and in mice macrophages that a heat shock of 42°C during 1 hour leads to an increase in the HSP70 expression 1 hour after the treatment and decreases the activity of the NLRP3 inflammasome. An overexpression of HSP70 was shown to mimic the effect of the heat shock, whereas an inhibition of the expression of HSP70 (via siRNA or knock-out mice) led to an increased activation of NLRP3.
A promising way to explain the activity of HSP70 is the ubiquitination state of the adaptator protein ASC.