PMID- 10623794 OWN - NLM STAT- MEDLINE DCOM- 20000210 LR - 20220223 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 164 IP - 2 DP - 2000 Jan 15 TI - Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. PG - 558-61 AB - 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. FAU - Ohashi, K AU - Ohashi K AD - German Diabetes Research Institute, Heinrich-Heine-University, Dusseldorf, Germany. FAU - Burkart, V AU - Burkart V FAU - Flohe, S AU - Flohe S FAU - Kolb, H AU - Kolb H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chaperonin 60) RN - 0 (Drosophila Proteins) RN - 0 (Ligands) RN - 0 (Macromolecular Substances) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, Cell Surface) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Animals MH - Chaperonin 60/*metabolism/physiology MH - *Drosophila Proteins MH - Humans MH - Ligands MH - Macromolecular Substances MH - Macrophages/immunology/metabolism MH - Membrane Glycoproteins/*metabolism/physiology MH - Mice MH - Mice, Inbred C3H MH - Mice, Inbred C57BL MH - Nitric Oxide/biosynthesis MH - Receptors, Cell Surface/*metabolism/physiology MH - Signal Transduction/immunology MH - Toll-Like Receptor 4 MH - Toll-Like Receptors MH - Tumor Necrosis Factor-alpha/biosynthesis EDAT- 2000/01/07 00:00 MHDA- 2000/01/07 00:01 CRDT- 2000/01/07 00:00 PHST- 2000/01/07 00:00 [pubmed] PHST- 2000/01/07 00:01 [medline] PHST- 2000/01/07 00:00 [entrez] AID - ji_v164n2p558 [pii] AID - 10.4049/jimmunol.164.2.558 [doi] PST - ppublish SO - J Immunol. 2000 Jan 15;164(2):558-61. doi: 10.4049/jimmunol.164.2.558.