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CUTTING EDGE |
*
Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division,
Vascular Research Division, Department of Pathology, Brigham and Women’s Hospital, and
Infectious Disease Program, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
Heat shock proteins (HSP), highly conserved across species, are generally viewed as intracellular proteins thought to serve protective functions against infection and cellular stress. Recently, we have reported the surprising finding that human and chlamydial HSP60, both present in human atheroma, can activate vascular cells and macrophages. However, the transmembrane signaling pathways by which extracellular HSP60 may activate cells remains unclear. CD14, the monocyte receptor for LPS, binds numerous microbial products and can mediate activation of monocytes/macrophages and endothelial cells, thus promoting the innate immune response. We show here that human HSP60 activates human PBMC and monocyte-derived macrophages through CD14 signaling and p38 mitogen-activated protein kinase, sharing this pathway with bacterial LPS. These findings provide further insight into the molecular mechanisms by which extracellular HSP may participate in atherosclerosis and other inflammatory disorders by activating the innate immune system.
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K. Chen, J. Lu, L. Wang, and Y.-H. Gan Mycobacterial heat shock protein 65 enhances antigen cross-presentation in dendritic cells independent of Toll-like receptor 4 signaling J. Leukoc. Biol., February 1, 2004; 75(2): 260 - 266. [Abstract] [Full Text] [PDF]
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 J C Cancino-Diaz, L Vargas-Rodriguez, N Grinberg-Zylberbaum, M A Reyes-Lopez, M L Dominguez-Lopez, A Pablo-Velazquez, and M E Cancino-Diaz High levels of IgG class antibodies to recombinant HSP60 kDa of Yersinia enterocolitica in sera of patients with uveitis Br J Ophthalmol, February 1, 2004; 88(2): 247 - 250. [Abstract] [Full Text] [PDF]
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A. P. Gobert, J.-C. Bambou, C. Werts, V. Balloy, M. Chignard, A. P. Moran, and R. L. Ferrero Helicobacter pylori Heat Shock Protein 60 Mediates Interleukin-6 Production by Macrophages via a Toll-like Receptor (TLR)-2-, TLR-4-, and Myeloid Differentiation Factor 88-independent Mechanism J. Biol. Chem., January 2, 2004; 279(1): 245 - 250. [Abstract] [Full Text] [PDF]
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T. Darville, J. M. O'Neill, C. W. Andrews Jr., U. M. Nagarajan, L. Stahl, and D. M. Ojcius Toll-Like Receptor-2, but Not Toll-Like Receptor-4, Is Essential for Development of Oviduct Pathology in Chlamydial Genital Tract Infection J. Immunol., December 1, 2003; 171(11): 6187 - 6197. [Abstract] [Full Text] [PDF]
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 B. OSTERUD and E. BJORKLID Role of Monocytes in Atherogenesis Physiol Rev, October 1, 2003; 83(4): 1069 - 1112. [Abstract] [Full Text] [PDF]
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B. Gao and M.-F. Tsan Recombinant Human Heat Shock Protein 60 Does Not Induce the Release of Tumor Necrosis Factor {alpha} from Murine Macrophages J. Biol. Chem., June 13, 2003; 278(25): 22523 - 22529. [Abstract] [Full Text] [PDF]
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H. Perschinka, M. Mayr, G. Millonig, C. Mayerl, R. van der Zee, S. G. Morrison, R. P. Morrison, Q. Xu, and G. Wick Cross-Reactive B-Cell Epitopes of Microbial and Human Heat Shock Protein 60/65 in Atherosclerosis Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1060 - 1065. [Abstract] [Full Text] [PDF]
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S. B. Flohe, J. Bruggemann, S. Lendemans, M. Nikulina, G. Meierhoff, S. Flohe, and H. Kolb Human Heat Shock Protein 60 Induces Maturation of Dendritic Cells Versus a Th1-Promoting Phenotype J. Immunol., March 1, 2003; 170(5): 2340 - 2348. [Abstract] [Full Text] [PDF]
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H. Cwiklinska, M. P. Mycko, O. Luvsannorov, B. Walkowiak, C. F. Brosnan, C. S. Raine, and K. W. Selmaj Heat shock protein 70 associations with myelin basic protein and proteolipid protein in multiple sclerosis brains Int. Immunol., February 1, 2003; 15(2): 241 - 249. [Abstract] [Full Text] [PDF]
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B. Gao and M.-F. Tsan Endotoxin Contamination in Recombinant Human Heat Shock Protein 70 (Hsp70) Preparation Is Responsible for the Induction of Tumor Necrosis Factor alpha Release by Murine Macrophages J. Biol. Chem., January 3, 2003; 278(1): 174 - 179. [Abstract] [Full Text] [PDF]
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K. H. Long, F. J. Gomez, R. E. Morris, and S. L. Newman Identification of Heat Shock Protein 60 as the Ligand on Histoplasma capsulatum That Mediates Binding to CD18 Receptors on Human Macrophages J. Immunol., January 1, 2003; 170(1): 487 - 494. [Abstract] [Full Text] [PDF]
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M. Breloer, S. H. More, A. Osterloh, F. Stelter, R. S. Jack, and A. v. Bonin Macrophages as main inducers of IFN-{gamma} in T cells following administration of human and mouse heat shock protein 60 Int. Immunol., November 1, 2002; 14(11): 1247 - 1253. [Abstract] [Full Text] [PDF]
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Y. Xie, C. Chen, M. A. Stevenson, P. E. Auron, and S. K. Calderwood Heat Shock Factor 1 Represses Transcription of the IL-1beta Gene through Physical Interaction with the Nuclear Factor of Interleukin 6 J. Biol. Chem., March 29, 2002; 277(14): 11802 - 11810. [Abstract] [Full Text] [PDF]
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J. Shaw, V. Grund, L. Durling, D. Crane, and H. D. Caldwell Dendritic Cells Pulsed with a Recombinant Chlamydial Major Outer Membrane Protein Antigen Elicit a CD4+ Type 2 Rather than Type 1 Immune Response That Is Not Protective Infect. Immun., March 1, 2002; 70(3): 1097 - 1105. [Abstract] [Full Text] [PDF]
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A. G. Pockley Heat Shock Proteins, Inflammation, and Cardiovascular Disease Circulation, February 26, 2002; 105(8): 1012 - 1017. [Full Text] [PDF]
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A. Ronaghy, B. J. Prakken, K. Takabayashi, G. S. Firestein, D. Boyle, N. J. Zvailfler, S. T. A. Roord, S. Albani, D. A. Carson, and E. Raz Immunostimulatory DNA Sequences Influence the Course of Adjuvant Arthritis J. Immunol., January 1, 2002; 168(1): 51 - 56. [Abstract] [Full Text] [PDF]
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X. H. Xu, P. K. Shah, E. Faure, O. Equils, L. Thomas, M. C. Fishbein, D. Luthringer, X.-P. Xu, T. B. Rajavashisth, J. Yano, et al. Toll-Like Receptor-4 Is Expressed by Macrophages in Murine and Human Lipid-Rich Atherosclerotic Plaques and Upregulated by Oxidized LDL Circulation, December 18, 2001; 104(25): 3103 - 3108. [Abstract] [Full Text] [PDF]
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H. Zheng, J. Dai, D. Stoilova, and Z. Li Cell Surface Targeting of Heat Shock Protein gp96 Induces Dendritic Cell Maturation and Antitumor Immunity J. Immunol., December 15, 2001; 167(12): 6731 - 6735. [Abstract] [Full Text] [PDF]
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J. C. Lewthwaite, A. R. M. Coates, P. Tormay, M. Singh, P. Mascagni, S. Poole, M. Roberts, L. Sharp, and B. Henderson Mycobacterium tuberculosis Chaperonin 60.1 Is a More Potent Cytokine Stimulator than Chaperonin 60.2 (Hsp 65) and Contains a CD14-Binding Domain Infect. Immun., December 1, 2001; 69(12): 7349 - 7355. [Abstract] [Full Text] [PDF]
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A. Billiau and P. Matthys Modes of action of Freund's adjuvants in experimental models of autoimmune diseases J. Leukoc. Biol., December 1, 2001; 70(6): 849 - 860. [Abstract] [Full Text] [PDF]
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S. H. More, M. Breloer, and A. von Bonin Eukaryotic heat shock proteins as molecular links in innate and adaptive immune responses: Hsp60-mediated activation of cytotoxic T cells Int. Immunol., September 1, 2001; 13(9): 1121 - 1127. [Abstract] [Full Text] [PDF]
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B. C. Berk Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms Physiol Rev, July 1, 2001; 81(3): 999 - 1030. [Abstract] [Full Text] [PDF]
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 H. Feng, Y. Zeng, L. Whitesell, and E. Katsanis Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity Blood, June 1, 2001; 97(11): 3505 - 3512. [Abstract] [Full Text] [PDF]
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R. J. Binder, K. M. Anderson, S. Basu, and P. K. Srivastava Cutting Edge: Heat Shock Protein gp96 Induces Maturation and Migration of CD11c+ Cells In Vivo J. Immunol., December 1, 2000; 165(11): 6029 - 6035. [Abstract] [Full Text] [PDF]
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C. Soulas, T. Baussant, J.-P. Aubry, Y. Delneste, N. Barillat, G. Caron, T. Renno, J.-Y. Bonnefoy, and P. Jeannin Cutting Edge: Outer Membrane Protein A (OmpA) Binds to and Activates Human Macrophages J. Immunol., September 1, 2000; 165(5): 2335 - 2340. [Abstract] [Full Text] [PDF]
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F. Castellino, P. E. Boucher, K. Eichelberg, M. Mayhew, J. E. Rothman, A. N. Houghton, and R. N. Germain Receptor-Mediated Uptake of Antigen/Heat Shock Protein Complexes Results in Major Histocompatibility Complex Class I Antigen Presentation via Two Distinct Processing Pathways J. Exp. Med., June 5, 2000; 191(11): 1957 - 1964. [Abstract] [Full Text] [PDF]
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 J S H Gaston Immunological basis of chlamydia induced reactive arthritis Sex Transm Inf, June 1, 2000; 76(3): 156 - 161. [Full Text] [PDF]
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R. M. Vabulas, P. Ahmad-Nejad, C. da Costa, T. Miethke, C. J. Kirschning, H. Hacker, and H. Wagner Endocytosed HSP60s Use Toll-like Receptor 2 (TLR2) and TLR4 to Activate the Toll/Interleukin-1 Receptor Signaling Pathway in Innate Immune Cells J. Biol. Chem., August 10, 2001; 276(33): 31332 - 31339. [Abstract] [Full Text] [PDF]
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S. Sasu, D. LaVerda, N. Qureshi, D. T. Golenbock, and D. Beasley Chlamydia pneumoniae and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation Circ. Res., August 3, 2001; 89(3): 244 - 250. [Abstract] [Full Text] [PDF]
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B. Dybdahl, A. Wahba, E. Lien, T. H. Flo, A. Waage, N. Qureshi, O. F.M. Sellevold, T. Espevik, and A. Sundan Inflammatory Response After Open Heart Surgery: Release of Heat-Shock Protein 70 and Signaling Through Toll-Like Receptor-4 Circulation, February 12, 2002; 105(6): 685 - 690. [Abstract] [Full Text] [PDF]
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