HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine
Top Cited Papers
- 1 April 2000
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 6 (4), 435-442
- https://doi.org/10.1038/74697
Abstract
Here, we demonstrate a previously unknown function for the 70-kDa heat-shock protein (HSP70) as a cytokine. HSP70 bound with high affinity to the plasma membrane, elicited a rapid intracellular calcium flux, activated nuclear factor (NF)-κB and upregulated the expression of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in 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-1β, IL-6 and TNF-α; and the other independent of CD14 but dependent on intracellular calcium, which resulted in an increase in TNF-α but not IL-1β or IL-6. These findings indicate that CD14 is a co-receptor for HSP70-mediated signaling in human monocytes and are indicative of an previously unrecognized function for HSP70 as an extracellular protein with regulatory effects on human monocytes, having a dual role as chaperone and cytokine.Keywords
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