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Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex

The Journal of Immunology · 2000 · Vol. 164(2) · pp. 558–561

Koji Ohashi✉(Deutsches Diabetes-Zentrum e.V.)Volker Burkart(Deutsches Diabetes-Zentrum e.V.)Stefanie B. Flohé(Deutsches Diabetes-Zentrum e.V.)Hubert Kolb(Deutsches Diabetes-Zentrum e.V.)

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Abstract

Human heat shock protein 60 (hsp60) elicits a potent proinflammatory response in cells of the innate immune system and therefore has been proposed as a danger signal of stressed or damaged cells. We report here that macrophages of C3H/HeJ mice, carrying a mutant Toll-like-receptor (Tlr) 4 are nonresponsive to hsp60. Both the induction of TNF-alpha and NO formation were found dependent on a functional Tlr4 whereas stimulation of macrophages by CpG DNA was Tlr4 independent. We conclude that Tlr4 mediates hsp60 signaling. This is the first report of a putative endogenous ligand of the Tlr4 complex.

Immune Response and Inflammation Heat shock proteins research ATP Synthase and ATPases ResearchTLR4Toll-like receptorHSP60ReceptorCell biologyEndogenyProinflammatory cytokineInnate immune systemHeat shock proteinBiology

MeSH terms

AnimalsHumansLigandsMacrophagesMembrane GlycoproteinsMice, Inbred C3HMice, Inbred C57BLNitric OxideReceptors, Cell SurfaceTumor Necrosis Factor-alphaSignal TransductionChaperonin 60Drosophila ProteinsMacromolecular SubstancesToll-Like Receptors

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