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

• DOI: 10.4049/jimmunol.164.2.558
• Publication Date: 2014-04-20T23:46:15Z
• Authors: Koji Ohashi; Volker Burkart; Stefanie Flohé; Hubert Kolb
• Keywords: Mice, Inbred C3H; Membrane Glycoproteins; Macromolecular Substances; Tumor Necrosis Factor-alpha; Macrophages; Toll-Like Receptors; Receptors, Cell Surface; Chaperonin 60; Ligands; Nitric Oxide; Mice, Inbred C57BL; Toll-Like Receptor 4; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Drosophila Proteins; Humans; Signal Transduction

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-α 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.