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Vabulas, R.M.* ; Ahmad-Nejad, P.* ; Ghose, S.* ; Kirschning, C.J.* ; Issels, R.D. ; Wagner, H.*

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

J. Biol. Chem. 277, 15107-15112 (2002)
Verlagsversion DOI PMC
Open Access Gold
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
Sprache englisch
Veröffentlichungsjahr 2002
HGF-Berichtsjahr 0
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Zeitschrift Journal of Biological Chemistry, The
Quellenangaben Band: 277, Heft: 17, Seiten: 15107-15112 Artikelnummer: , Supplement: ,
Verlag American Society for Biochemistry and Molecular Biology
Begutachtungsstatus Peer reviewed
Institut(e) CCG Tumor Therapy with Hyperthermia (IMI-KTH)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-521100-001
PubMed ID 11842086
Erfassungsdatum 2002-09-09
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