Details

Autor(en) / Beteiligte

• Vabulas, R M
• Ahmad-Nejad, P
• da Costa, C
• Miethke, T
• Kirschning, C J
• Häcker, H
• Wagner, H

Titel

Endocytosed HSP60s Use Toll-like Receptor 2 (TLR2) and TLR4 to Activate the Toll/Interleukin-1 Receptor Signaling Pathway in Innate Immune Cells

Ist Teil von

• The Journal of biological chemistry, 2001-08, Vol.276 (33), p.31332-31339

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2001

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Heat shock proteins (HSPs) require no adjuvant to confer immunogenicity to bound peptides, as if they possessed an intrinsic “danger” signature. To understand the proinflammatory nature of HSP, we analyzed signaling induced by human and chlamydial HSP60. We show that both HSP60s activate the stress-activated protein kinases p38 and JNK1/2, the mitogen-activated protein kinases ERK1/2, and the I-κB kinase (IKK). Activation of JNK and IKK proceeds via the Toll/IL-1 receptor signaling pathway involving MyD88 and TRAF6. Human fibroblasts transfected with TLR2 or TLR4 plus MD-2 gain responsiveness to HSP60, while TLR2- or TLR4-defective cells display impaired responses. Initiation of signaling requires endocytosis of HSP60 that is effectively inhibited by serum component(s). The results revealed that adjuvanticity of HSP60 operates similar to that of classical pathogen-derived ligands.