Heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex

Human heat shock protein 60 (hsp60) elicits a potent proinflammatory respon se 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 macrophag es of C3H/HeJ mice, carrying a mutant Toll-like-receptor (Tlr) 4 are nonres ponsive to hsp60. Both the induction of TNF-alpha and NO formation were fou nd 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 comple x.