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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
HSP70 as Endogenous Stimulus of the Tol/Interleukin-1 Receptor Signal Pathway.
J. Biol. Chem. 277, 15107-15112 (2002)
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 that TLR2 and TLR4 confer responsiveness to HSP70 in 293T fibroblasts. The expanding list of endogenous ligands able to activate the ancient Toll/IL-1 receptor signal pathway is in line with the danger hypothesis" proposing that the innate immune system senses danger signals even if they originate from self."
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
HEAT-SHOCK PROTEINS; TOLL-LIKE RECEPTOR-4; DENDRITIC CELLS; HOST-DEFENSE; MATURATION; INNATE; IMMUNITY; SYSTEM; DEATH; MECHANISM
ISSN (print) / ISBN
0021-9258
e-ISSN
1083-351X
Zeitschrift
Journal of Biological Chemistry, The
Quellenangaben
Band: 277,
Heft: 17,
Seiten: 15107-15112
Verlag
American Society for Biochemistry and Molecular Biology
Begutachtungsstatus
Peer reviewed
Institut(e)
CCG Tumor Therapy with Hyperthermia (IMI-KTH)