A. Asea et al., HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine, NAT MED, 6(4), 2000, pp. 435-442
Citations number
44
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Here, we demonstrate a previously unknown function for the 70-kDa heat-shoc
k protein (HSP70) as a cytokine. HSP70 bound with high affinity to the plas
ma membrane, elicited a rapid intracellular calcium flux, activated nuclear
factor (NF)-kappaB and upregulated the expression of pro-inflammatory cyto
kines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 i
n human monocytes. Furthermore, two different signal transduction pathways
were activated by exogenous HSP70: one dependent on CD14 and intracellular
calcium, which resulted in increased IL-1 beta, IL-6 and TNF-alpha; and the
other independent of CD14 but dependent on intracellular calcium, which re
sulted in an increase in TNF-alpha but not IL-1 beta or IL-6. These finding
s indicate that CD14 is a co-receptor for HSP70-mediated signaling in human
monocytes and are indicative of an previously unrecognized function for HS
P70 as an extracellular protein with regulatory effects on human monocytes,
having a dual role as chaperone and cytokine.