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The Journal of Immunology, 2000, 164: 558-561.
Copyright © 2000 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex1

Koji Ohashi, Volker Burkart, Stefanie Flohé and Hubert Kolb2

German Diabetes Research Institute, Heinrich-Heine-University, Düsseldorf, Germany

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.




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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. T. Borchers, N. L. Harris, S. C. Wesselkamper, M. Vitucci, and D. Cosman
NKG2D ligands are expressed on stressed human airway epithelial cells
Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L222 - L231.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
O. Equils, D. Lu, M. Gatter, S. S. Witkin, C. Bertolotto, M. Arditi, J. A. McGregor, C. F. Simmons, and C. J. Hobel
Chlamydia Heat Shock Protein 60 Induces Trophoblast Apoptosis through TLR4
J. Immunol., July 15, 2006; 177(2): 1257 - 1263.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
A. Shimamoto, A. J. Chong, M. Yada, S. Shomura, H. Takayama, A. J. Fleisig, M. L. Agnew, C. R. Hampton, C. L. Rothnie, D. J. Spring, et al.
Inhibition of Toll-like Receptor 4 With Eritoran Attenuates Myocardial Ischemia-Reperfusion Injury
Circulation, July 4, 2006; 114(1_suppl): I-270 - I-274.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
B. Henderson, E. Allan, and A. R. M. Coates
Stress Wars: the Direct Role of Host and Bacterial Molecular Chaperones in Bacterial Infection
Infect. Immun., July 1, 2006; 74(7): 3693 - 3706.
[Full Text] [PDF]

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 Neuro Oncol DukeHome page
S. F. Hussain, D. Yang, D. Suki, K. Aldape, E. Grimm, and A. B. Heimberger
The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses
Neuro-oncol, July 1, 2006; 8(3): 261 - 279.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
P. Rallabhandi, J. Bell, M. S. Boukhvalova, A. Medvedev, E. Lorenz, M. Arditi, V. G. Hemming, J. C. G. Blanco, D. M. Segal, and S. N. Vogel
Analysis of TLR4 Polymorphic Variants: New Insights into TLR4/MD-2/CD14 Stoichiometry, Structure, and Signaling
J. Immunol., July 1, 2006; 177(1): 322 - 332.
[Abstract] [Full Text] [PDF]

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 Int ImmunolHome page
M. K. Mohammad, M. Morran, B. Slotterbeck, D. W. Leaman, Y. Sun, H. v. Grafenstein, S.-C. Hong, and M. F. McInerney
Dysregulated Toll-like receptor expression and signaling in bone marrow-derived macrophages at the onset of diabetes in the non-obese diabetic mouse
Int. Immunol., July 1, 2006; 18(7): 1101 - 1113.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
P. G. Tipping
Toll-Like Receptors: The Interface between Innate and Adaptive Immunity
J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1769 - 1771.
[Full Text] [PDF]

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 Innate ImmunityHome page
A. E. Medvedev, I. Sabroe, J. D. Hasday, and S. N. Vogel
Invited review: Tolerance to microbial TLR ligands: molecular mechanisms and relevance to disease
Innate Immunity, June 1, 2006; 12(3): 133 - 150.
[Abstract] [PDF]

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 J. Immunol.Home page
M. F. Roelofs, W. C. Boelens, L. A. B. Joosten, S. Abdollahi-Roodsaz, J. Geurts, L. U. Wunderink, B. W. Schreurs, W. B. van den Berg, and T. R. D. J. Radstake
Identification of Small Heat Shock Protein B8 (HSP22) as a Novel TLR4 Ligand and Potential Involvement in the Pathogenesis of Rheumatoid Arthritis.
J. Immunol., June 1, 2006; 176(11): 7021 - 7027.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
Y. Zhai, L. Meng, F. Gao, Y. Wang, R. W. Busuttil, and J. W. Kupiec-Weglinski
CD4+ T Regulatory Cell Induction and Function in Transplant Recipients after CD154 Blockade Is TLR4 Independent
J. Immunol., May 15, 2006; 176(10): 5988 - 5994.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
O. A. Harari, P. Alcaide, D. Ahl, F. W. Luscinskas, and J. K. Liao
Absence of TRAM Restricts Toll-Like Receptor 4 Signaling in Vascular Endothelial Cells to the MyD88 Pathway
Circ. Res., May 12, 2006; 98(9): 1134 - 1140.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
I. Jou, J. H. Lee, S. Y. Park, H. J. Yoon, E.-H. Joe, and E. J. Park
Gangliosides Trigger Inflammatory Responses via TLR4 in Brain Glia
Am. J. Pathol., May 1, 2006; 168(5): 1619 - 1630.
[Abstract] [Full Text] [PDF]

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 Int ImmunolHome page
S.-i. Yokota, S. Minota, and N. Fujii
Anti-HSP auto-antibodies enhance HSP-induced pro-inflammatory cytokine production in human monocytic cells via Toll-like receptors
Int. Immunol., April 1, 2006; 18(4): 573 - 580.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. Szalay, T. Shimizu, T. Suzuki, H.-P. Yu, M. A. Choudhry, M. G. Schwacha, L. W. Rue III, K. I. Bland, and I. H. Chaudry
Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R812 - R818.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
C. M. O'Connell, I. A. Ionova, A. J. Quayle, A. Visintin, and R. R. Ingalls
Localization of TLR2 and MyD88 to Chlamydia trachomatis Inclusions: EVIDENCE FOR SIGNALING BY INTRACELLULAR TLR2 DURING INFECTION WITH AN OBLIGATE INTRACELLULAR PATHOGEN
J. Biol. Chem., January 20, 2006; 281(3): 1652 - 1659.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
E. F. Cohn, C. Nathan, D. Radzioch, H. Yu, Z. Xiang, and A. Ding
Abrupt Expression of TLR4 in TLR4-Deficient Macrophages Imposes a Selective Disadvantage: Genetic Evidence for TLR4-Dependent Responses to Endogenous, Nonmicrobial Stimuli
J. Immunol., January 15, 2006; 176(2): 1185 - 1194.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
Y. Chen and R. W. Currie
Small interfering RNA knocks down heat shock factor-1 (HSF-1) and exacerbates pro-inflammatory activation of NF-{kappa}B and AP-1 in vascular smooth muscle cells
Cardiovasc Res, January 1, 2006; 69(1): 66 - 75.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y. Ma, V. Temkin, H. Liu, and R. M. Pope
NF-{kappa}B Protects Macrophages from Lipopolysaccharide-induced Cell Death: THE ROLE OF CASPASE 8 AND RECEPTOR-INTERACTING PROTEIN
J. Biol. Chem., December 23, 2005; 280(51): 41827 - 41834.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
T. Ha, Y. Li, F. Hua, J. Ma, X. Gao, J. Kelley, A. Zhao, G. E. Haddad, D. L. Williams, I. William Browder, et al.
Reduced cardiac hypertrophy in toll-like receptor 4-deficient mice following pressure overload
Cardiovasc Res, November 1, 2005; 68(2): 224 - 234.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Makino, G. G. Whitehead, C.-L. Lien, S. Kim, P. Jhawar, A. Kono, Y. Kawata, and M. T. Keating
Heat-shock protein 60 is required for blastema formation and maintenance during regeneration
PNAS, October 11, 2005; 102(41): 14599 - 14604.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
C. A. Petersen, K. A. Krumholz, and B. A. Burleigh
Toll-Like Receptor 2 Regulates Interleukin-1{beta}-Dependent Cardiomyocyte Hypertrophy Triggered by Trypanosoma cruzi
Infect. Immun., October 1, 2005; 73(10): 6974 - 6980.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
M. Cohen-Sfady, G. Nussbaum, M. Pevsner-Fischer, F. Mor, P. Carmi, A. Zanin-Zhorov, O. Lider, and I. R. Cohen
Heat Shock Protein 60 Activates B Cells via the TLR4-MyD88 Pathway
J. Immunol., September 15, 2005; 175(6): 3594 - 3602.
[Abstract] [Full Text] [PDF]

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 JEMHome page
M. J. Smyth, J. Swann, E. Cretney, N. Zerafa, W. M. Yokoyama, and Y. Hayakawa
NKG2D function protects the host from tumor initiation
J. Exp. Med., September 6, 2005; 202(5): 583 - 588.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
I. Olsen, P. Boysen, S. Kulberg, J. C. Hope, G. Jungersen, and A. K. Storset
Bovine NK Cells Can Produce Gamma Interferon in Response to the Secreted Mycobacterial Proteins ESAT-6 and MPP14 but Not in Response to MPB70
Infect. Immun., September 1, 2005; 73(9): 5628 - 5635.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
A. M. McCord, A. W. O. Burgess, M. J. Whaley, and B. E. Anderson
Interaction of Bartonella henselae with Endothelial Cells Promotes Monocyte/Macrophage Chemoattractant Protein 1 Gene Expression and Protein Production and Triggers Monocyte Migration
Infect. Immun., September 1, 2005; 73(9): 5735 - 5742.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
F. J. Quintana and I. R. Cohen
Heat Shock Proteins as Endogenous Adjuvants in Sterile and Septic Inflammation
J. Immunol., September 1, 2005; 175(5): 2777 - 2782.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
H. S. Youn, J. Y. Lee, K. A. Fitzgerald, H. A. Young, S. Akira, and D. H. Hwang
Specific Inhibition of MyD88-Independent Signaling Pathways of TLR3 and TLR4 by Resveratrol: Molecular Targets Are TBK1 and RIP1 in TRIF Complex
J. Immunol., September 1, 2005; 175(5): 3339 - 3346.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
X. Yang, D. Coriolan, V. Murthy, K. Schultz, D. T. Golenbock, and D. Beasley
Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling
Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1069 - H1076.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
G. Foteinos, A. R. Afzal, K. Mandal, M. Jahangiri, and Q. Xu
Anti-Heat Shock Protein 60 Autoantibodies Induce Atherosclerosis in Apolipoprotein E-Deficient Mice via Endothelial Damage
Circulation, August 23, 2005; 112(8): 1206 - 1213.
[Abstract] [Full Text] [PDF]


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