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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chaperonin 60 / metabolism*
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Chaperonin 60 / physiology
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Drosophila Proteins*
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Humans
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Ligands
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Macromolecular Substances
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Macrophages / immunology
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Macrophages / metabolism
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Membrane Glycoproteins / metabolism*
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Nitric Oxide / biosynthesis
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Receptors, Cell Surface / metabolism*
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Receptors, Cell Surface / physiology
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Signal Transduction / immunology
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Toll-Like Receptor 4
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Chaperonin 60
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Drosophila Proteins
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Ligands
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Macromolecular Substances
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Membrane Glycoproteins
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Receptors, Cell Surface
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TLR4 protein, human
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Toll-Like Receptor 4
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha
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Nitric Oxide