articleJournal of Biological ChemistryApr 1, 2002HYBRID OA

HSP70 as Endogenous Stimulus of the Toll/Interleukin-1 Receptor Signal Pathway

Technical University of Munich · Institute of Medical Microbiology and Hygiene · +2 more institutions

PubMed
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Abstract

Human heat-shock protein (HSP)70 activates innate immune cells and hence requires no additional adjuvants to render bound peptides immunogenic. Here we tested the assumption that endogenous HSP70 activates the Toll/IL-1 receptor signal pathway similar to HSP60 and pathogen-derived molecular patterns. We show that HSP70 induces interleukin-12 (IL-12) and endothelial cell-leukocyte adhesion molecule-1 (ELAM-1) promoters in macrophages and that this is controlled by MyD88 and TRAF6. Furthermore, HSP70 causes MyD88 relocalization and MyD88-deficient dendritic cells do not respond to HSP70 with proinflammatory cytokine production. Using the system of genetic complementation with Toll-like receptors (TLR) we found…

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