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Cutting Edge: Heat Shock Protein (HSP) 60 Activates the Innate Immune Response: CD14 Is an Essential Receptor for HSP60 Activation of Mononuclear Cells¹

Amir Kol^*, Andrew H. Lichtman, Robert W. Finberg, Peter Libby^*, and Evelyn A. Kurt-Jones^2,

^* 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

	Abstract

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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.

	Introduction

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There is increasing interest in the role of nontraditional mediators of inflammation in atherosclerosis (1). Recent studies from our laboratory have shown that chlamydial and human heat shock protein 60 (HSP60)³ colocalize in human atheroma (2), and either HSP60 induces adhesion molecule and cytokine production by human vascular cells and macrophages, in a pattern similar to that induced by Escherichia coli LPS (3, 4). These results suggested that HSP60 and LPS might share similar signaling mechanisms. CD14 is the major high-affinity receptor for bacterial LPS on the cell membrane of mononuclear cells and macrophages (5, 6). In addition to LPS, CD14 functions as a signaling receptor for other microbial products, including peptidoglycan from Gram-positive bacteria and mycobacterial lipoarabinomann (7, 8). CD14 is considered a pattern recognition receptor for microbial Ags and, with Toll-like receptor (TLR) proteins, an important mediator of innate immune responses to infection (9, 10, 11, 12, 13, 14). We have examined the role of CD14 in the response of human monocytes and macrophages to HSP60.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
Reagents

Recombinant human HSP60 was purchased from StressGen Biotechnologies Corporation (Victoria, BC, Canada). E. coli LPS, PMA, and polymyxin B were purchased from Sigma (St. Louis, MO). CD14-blocking mAb (clone MY4) was purchased from Coulter Immunology (Hialeah, FL). Recombinant chlamydial HSP60 was purified as previously described (3) and passed over a commercial endotoxin removal cartridge (END-X; Associates of Cape Cod, Wood’s Hole, MA) following the manufacturer directions. Endotoxin levels were determined using a BioWhittaker Limulus amebocyte lysate assay kit (Walkersville, MD) and resistance to heat-treatment (100°C, 20 min). (Different preparations of purified chlamydial HSP60 varied in their endotoxin content and heat resistance. In our previous studies, the macrophage-stimulating activity of the purified chlamydial HSP60 was completely heat labile (3). The preparation used in these studies was partially heat-resistant before removing residual endotoxin.)

Cell culture and analysis of conditioned medium

PBMC were isolated from leukopacs of healthy donors by gradient centrifugation, and human macrophages were subsequently isolated by adherence and culture in 2% human serum for 10 days, as previously described (3). Human astrocytoma cells (U373 MG) stably transfected with human CD14 cDNA (U373-CD14) and control U373 cells were provided by Dr. Douglas Golenbock (Boston University Medical Center) (15). Culture supernatants were harvested 18–24 h after stimulation, and IL-6 secretion was determined by sandwich ELISA (Endogen, Cambridge, MA). Data are expressed as the mean ± SD of duplicate determination and are representative of 8–10 separate experiments for each cell type.

p38 mitogen-activated protein kinase (MAPK) assay

The activation of p38 MAPK was determined using an assay kit (New England Biolabs, Beverly, MA). Briefly, dually phosphorylated p38 MAPK was immunoprecipitated from cell lysates and subjected to in vitro kinase assay with activating transcription factor 2 (ATF-2) as a kinase substrate. ATF-2 phosphorylation was determined by SDS-PAGE and Western blot analysis of the in vitro kinase reaction using a phospho-ATF-2-specific Ab.

NF-B activation in transfected hamster cells

Chinese hamster ovary (CHO) cells stably transfected with human CD14 and a reporter plasmid (NF-B response element of the E-selectin promoter fused to the coding region of the human CD25 gene) were provided by Dr. Douglas Golenbock (16). NF-B activation was measured by flow cytometric analysis of cells stained with anti-CD25 mAb (Coulter Immunology) or an isotype control (MOPC21; Sigma) followed by PE-labeled goat anti-mouse IgG antiserum (Sigma). LPS responsiveness in these cells is dependent on CD14 expression (17). Data are representative of five separate experiments.

	Results

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Human HSP60 stimulation of cytokine synthesis is CD14 dependent and not due to endotoxin

We tested the hypothesis that HSP60 activates mononuclear cells and macrophages through CD14 signaling. As a measure of cellular activation, we assessed the cellular production of IL-6, an important proinflammatory cytokine and mediator of the acute-phase response (18).

Human HSP60 induced the synthesis of IL-6 by PBMC (Fig. 1A). HSP60 induced IL-6 similarly to optimal concentrations of E. coli LPS (Fig. 1B). Preincubation of PBMC with an anti-CD14 Ab blocked IL-6 production in response to either HSP60 or E. coli LPS. PMA also induced IL-6 production, but the anti-CD14 Ab did not inhibit this response (Fig. 1C).

View larger version (32K): [in this window] [in a new window]   FIGURE 1. HSP60 induces IL-6 production by human PBMC in a CD14-dependent manner. PBMC were isolated from leukopacs of healthy donors. To define the optimal concentrations of HSP60 (StressGen) and E. coli LPS (Sigma), we tested a range of concentrations (0.1–3 µg/ml for HSP60 and 1 ng/ml to 1 µg/ml for E. coli LPS, optimal concentrations chosen for this study are shown). PBMC were incubated with medium only (unstimulated control), human HSP60 (1 µg/ml), E. coli LPS (10 ng/ml), or PMA (Sigma) (100 ng/ml). Supernatants were harvested 18 h later and analyzed for IL-6 by sandwich ELISA (Endogen). Where indicated, PBMC were treated with anti-CD14 Ab (10 µg/ml) (MY4 clone; Coulter Immunology) or polymyxin B (10 µg/ml) (Sigma) for 1 h before the addition of stimulant. In the indicated cultures, HSP60, LPS, and PMA were heat treated (100°C, 20 min) before addition to PBMC.

The results obtained with blocking studies suggest that CD14 is critical to the activation of human monocyte/macrophages by HSP60. To confirm this interpretation, we examined the role of CD14 in the response to HSP60 using a human astrocytoma cell line, U373. U373 cells constitutively lack responsiveness to LPS, but acquire this property when stably transfected with a human CD14 cDNA (U373-CD14) (15) or when cultured in the presence of recombinant soluble CD14 (7, 21). Nontransfected U373 responded to neither HSP60 nor E. coli LPS, but were activated by PMA (Fig. 2, upper panels). U373 cells transfected with CD14 acquired the ability to produce IL-6 when exposed to either HSP60 or E. coli LPS (Fig. 2, lower panels). The anti-CD14 Ab inhibited only the responses to HSP60 and to E. coli LPS, but not to PMA (Fig. 2, upper and lower panels), supporting the role of CD14 as a crucial receptor for HSP60 on mononuclear phagocytes.

View larger version (27K): [in this window] [in a new window]   FIGURE 2. U373 cells transfected with human CD14 produce IL-6 in response to HSP60. Human astrocytoma cells (U373 MG; American Type Culture Collection, Manassas, VA), stably transfected with human CD14 (U373-CD14), were incubated with medium only (unstimulated control), human HSP60 (1 µg/ml), E. coli LPS (100 ng/ml), or PMA (100 ng/ml). Culture supernatants were harvested 18h later and analyzed for IL-6 by sandwich ELISA. Preincubation of U373-CD14 cells for 1 h with anti-CD14 Ab (MY4 clone, 10 µg/ml) inhibited IL-6 production in response to either HSP60 or E. coli LPS, but not to PMA (lower panels). Control, nontransfected cells responded to PMA only (upper panels).

We further examined the intracellular activation pathways used by HSP60. The CD14-dependent activation of human monocytes induced by LPS involves the dual phosphorylation and activation of p38 MAPK (22). PBMC were treated with either HSP60 or E. coli LPS, and p38 MAPK activation was determined by immunoprecipitation of dual-phosphorylated p38 and in vitro kinase assay measuring phosphorylation of the p38 substrate, ATF-2. Kinetic analysis showed that HSP60 and E. coli LPS induced similar patterns of p38 MAPK activation, with maximal activation of p38 observed within 15–30 min and a return to basal levels by 60 min (Fig. 3). In other experiments, pretreatment of PBMC with SB202190, a selective p38 MAPK antagonist (23), inhibited IL-6 production in response to either HSP60 or E. coli LPS by >90% (data not shown).

View larger version (23K): [in this window] [in a new window]   FIGURE 3. HSP60 activates p38 MAPK in PBMC. PBMC were incubated with human HSP60 (1 µg/ml) or E. coli LPS (10 ng/ml) for the indicated times and lysed in buffer containing Nonidet P-40 and phosphatase inhibitors. p38 MAPK activation was determined using a New England Biolabs assay kit. Briefly, dually phosphorylated p38 MAPK was immunoprecipitated from cell lysates and subjected to in vitro kinase assay with ATF-2 as a kinase substrate. ATF-2 phosphorylation was determined by SDS-PAGE and Western blot analysis of the in vitro kinase reaction and detected using a phospho-ATF-2-specific Ab (Phospho-ATF-2). Western blot analysis of Igs in the immunoprecipitates was performed to ensure equal protein loading (IgG control).

We have also examined the ability of chlamydial HSP60 to stimulate monocytes. Recombinant chlamydial HSP60 was purified from E. coli as described (3). The initial preparation of chlamydial HSP60 contained 10 EU/µg of endotoxin in the Limulus amebocyte lysate assay. After passage through an endotoxin removal cartridge (END-X; Associates of Cape Cod), the endotoxin level was reduced to <1.5 EU/µg. The endotoxin-depleted chlamydial HSP60 stimulated U373-CD14 cytokine secretion (Fig. 4A). Before endotoxin depletion, there was a heat-resistant activity in the purified chlamydial HSP60. This component was removed by passage over an endotoxin depletion column. The remaining cytokine-stimulating activity was entirely heat labile (Fig. 4A). Thus, chlamydial HSP60 directly stimulates cytokine secretion in U373-CD14 cells in the absence of endotoxin. Human PBMC also responded to a heat-labile component of chlamydial HSP60, and the response was blocked by anti-CD14 pretreatment (Fig. 4B).

View larger version (37K): [in this window] [in a new window]   FIGURE 4. Chlamydial HSP60 induces IL-6 production. A, Recombinant chlamydial HSP60 was purified from E. coli. Purified chlamydial HSP60 was depleted of endotoxin by passage over an END-X (Associates of Cape Cod) endotoxin removal cartridge. Endotoxin levels in the initial and endotoxin-depleted chlamydial HSP60 preparation were determined by Limulus amebocyte lysate assay (BioWhittaker). The initial chlamydial HSP60 preparation contained 10 EU/µg endotoxin. After endotoxin depletion, the purified HSP60 contained <1.5 EU/µg endotoxin. U373-CD14 cells were incubated with medium only (unstimulated control) or chlamydial HSP60 (3 µg/ml). Supernatants were harvested 18 h later and analyzed for IL-6 by sandwich ELISA (Endogen). Where indicated, chlamydial HSP60 preparations were heat treated (100°C, 20 min) before addition to cells. B, Human PBMC were stimulated with chlamydial HSP60, as described in Fig. 1. IL-6 secretion was measured by ELISA 18 h later. Where indicated, PBMC were preincubated with MY4 anti-CD14 Ab before the addition of chlamydial HSP60 (1 µg/ml) or LPS (10 ng/ml).

Neither human nor chlamydial HSP60 activated NF-B in a hamster reporter cell line: CD14 is necessary but not sufficient for HSP60 signaling

We examined the ability of human and chlamydial HSP60 to activate NF-B in hamster cells transfected with human CD14 and an NF-B reporter gene. Transfection with human CD14 is sufficient to confer LPS responsiveness on CHO cells detected by increased CD25 expression measured by flow cytometry (Fig. 5) (16, 17). Human HSP60 and chlamydial HSP60 did not induce CD25 expression in the reporter cell line, although the cells were responsive to LPS (Fig. 5). This is in contrast to our results with transfected U373 cells (Fig. 3), where transfection with CD14 is sufficient to confer responsiveness to HSP60. Thus, CD14 expression in a human (U373) but not a rodent (CHO) cell line is sufficient to confer HSP60 responsiveness, suggesting that additional coreceptor proteins are required for HSP60 signaling in hamster cells. These experiments also demonstrate that the requirements for responses to LPS and HSP60 are distinct and that the activity of the recombinant HSP60 proteins is not due to endotoxin.

View larger version (28K): [in this window] [in a new window]   FIGURE 5. LPS activates NF-B in CHO cells, but human and chlamydial HSP60 do not activate NF-B. NF-B activation was measured using a CHO cell reporter line. These CHO cells are stably transfected with human CD14 and a NF-B reporter gene consisting of an E-selectin NF-B promoter sequence fused to the coding region of the human CD25 gene. The CHO-CD14 cells were incubated in medium alone or stimulated with LPS (10 ng/ml; top panel), human HSP60 (10 µg/ml; middle panel), or chlamydial HSP60 (3 µg/ml; bottom panel) for 18 h. After stimulation, the CHO cells were harvested with EDTA and incubated with monoclonal anti-CD25 Ab or isotype control Ab (CTRL), followed by PE-labeled goat anti-mouse antiserum. CD25 expression was determined by flow cytometry.

	Discussion

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Our studies with human CD14-transfected U373 (human) and CHO (hamster) cells demonstrate that CD14 is necessary but not sufficient for cellular responsiveness to HSP60, suggesting that human but not hamster cells express an important coreceptor for HSP60 signaling. TLRs have recently been shown to be important components of the CD14 signaling complex. TLRs are transmembrane proteins that contain large extracellular leucine-rich domains and intracellular domains that are homologous to the intracellular domain of the IL-1 receptor (12, 30). TLR2 and TLR4 have both been shown to contribute to the LPS response of human cells (9, 10, 31). Hamsters have recently been shown to have a null mutation in their TLR2 gene and therefore fail to express TLR2 protein on their cells (32). Despite the lack of TLR2, hamster cells are LPS responsive, suggesting that LPS responses in rodents may be primarily transduced through TLR4 (11, 32, 33, 34). In contrast, hamster cell responses to other CD14 ligands are TLR2 dependent, i.e., CHO cells are unresponsive to peptidoglycan and Gram-positive bacteria but acquire responsiveness when transfected with human TLR2 (and CD14) (35). We are currently investigating the role of Toll-like proteins in the response of cells to HSP60.

HSP may play a central role in the innate immune response to microbial infections. Because both microbes and stressed or injured host cells produce abundant HSP (36), and dying cells likely release these proteins, it is conceivable that HSP furnish signals that inform the innate immune system of the presence of infection and cell damage. The findings reported here, that human HSP60 induces IL-6 production by mononuclear cells and macrophages via the CD14, supports this hypothesis, suggesting that human HSP60 may act together with LPS or other microbial products to provoke innate immune responses.

Inflammation and immunity can contribute to the pathogenesis and complications of atherosclerosis (37). Moreover, the search for novel risk factors for atherosclerosis has revived the concept that microbial products might substantially contribute to the inflammatory reaction in the atheromatous vessel wall (38, 39). We have shown that chlamydial HSP60 colocalizes with human HSP60 in the macrophages of human atheroma (2). Therefore, bacterial and human HSP60, released from dying or injured cells during atherogenesis (40) or myocardial injury (41), may further promote local inflammation and possibly activate the innate immune system. Previous reports that immunization with mycobacterial HSP65 enhances atheroma formation in rabbits (42), have suggested an important role for HSPs in atherogenesis, particularly because the high degree of homology between HSPs of the same m.w. among different species might stimulate autoimmunity (43).

In conclusion, our findings, that CD14 mediates cellular activation induced by human HSP60 provide further insight into the molecular mechanisms by which HSP may activate the innate immune system and participate in atherogenesis and other inflammatory disorders.

	Acknowledgments

 
We thank Carolyn Come, Marysia Muszynski, Lana Popova, and Laura Kwinn for excellent technical assistance.

	Footnotes

 
¹ This work was supported in part by National Institutes of Health Grants PO1HL48743 (to A.H.L. and P.L.), P50-HL56985 (to A.H.L.), RO1AI31628, and RO1AI39576 (to R.W.F.). A.K. is the recipient of a Fulbright Scholarship.

² Address correspondence and reprint requests to Dr. Evelyn A. Kurt-Jones, Infectious Disease Program D1440, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. E-mail address:

³ Abbreviations used in this paper: HSP, heat shock protein; TLR, toll-like receptor; MAPK, mitogen-activated protein kinase; ATF, activating transcription factor; CHO, Chinese hamster ovary.

Received for publication September 27, 1999. Accepted for publication November 4, 1999.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Libby, P.. 1996. Atheroma: more than mush. Lancet 348:(Suppl. 1):s4.
2. Kol, A., G. K. Sukhova, A. H. Lichtman, P. Libby. 1998. Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor- and matrix metalloproteinase expression. Circulation 98:300.[Abstract/Free Full Text]
3. Kol, A., T. Bourcier, A. H. Lichtman, P. Libby. 1999. Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J. Clin. Invest. 103:571.[Medline]
4. Verdegaal, M. E., S. T. Zegveld, R. van Furth. 1996. Heat shock protein 65 induces CD62e, CD106, and CD54 on cultured human endothelial cells and increases their adhesiveness for monocytes and granulocytes. J. Immunol. 157:369.[Abstract]
5. Ulevitch, R. J.. 1993. Recognition of bacterial endotoxins by receptor-dependent mechanisms. Adv. Immunol. 53:267.[Medline]
6. Wright, S. D., R. A. Ramos, P. S. Tobias, R. J. Ulevitch, J. C. Mathison. 1990. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249:1431.[Abstract/Free Full Text]
7. Savedra, R., Jr., R. L. Delude, R. R. Ingalls, M. J. Fenton, and D. T. Golenbock. 1996. Mycobacterial lipoarabinomannan recognition requires a receptor that shares components of the endotoxin signaling system. J. Immunol. 157:2549.
8. Weidemann, B., J. Schletter, R. Dziarski, S. Kusumoto, F. Stelter, E. T. Rietschel, H. D. Flad, A. J. Ulmer. 1997. Specific binding of soluble peptidoglycan and muramyldipeptide to CD14 on human monocytes. Infect. Immun. 65:858.[Abstract]
9. Kirschning, C. J., H. Wesche, T. Merrill Ayres, M. Rothe. 1998. Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. J. Exp. Med. 188:2091.[Abstract/Free Full Text]
10. Yang, R.-B., M. R. Mark, A. Gray, A. Huang, M. H. Xie, M. Zhang, A. Goddard, W. I. Wood, A. L. Gurney, P. J. Godowski. 1998. Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature 395:284.[Medline]
11. Poltorak, A., X. He, I. Smirnova, M. Y. Liu, C. V. Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, et al 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085.[Abstract/Free Full Text]
12. Medzhitov, R., P. Preston-Hurlburt, Jr C. A. Janeway. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394.[Medline]
13. Medzhitov, R., Jr C. A. Janeway. 1997. Innate immunity: the virtues of a nonclonal system of recognition. Cell 91:295.[Medline]
14. Pugin, J., I. D. Heumann, A. Tomasz, V. V. Kravchenko, Y. Akamatsu, M. Nishijima, M. P. Glauser, P. S. Tobias, R. J. Ulevitch. 1994. CD14 is a pattern recognition receptor. Immunity 1:509.[Medline]
15. Solomon, K. R., E. A. Kurt-Jones, R. A. Saladino, A. M. Stack, I. F. Dunn, M. Ferretti, D. Golenbock, G. R. Fleisher, R. W. Finberg. 1998. Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide. J. Clin. Invest. 102:2019.[Medline]
16. Delude, R. L., A. Yoshimura, R. R. Ingalls, D. T. Golenbock. 1998. Construction of a lipopolysaccharide reporter cell line and its use in identifying mutants defective in endotoxin, but not TNF-, signal transduction. J. Immunol. 161:3001.[Abstract/Free Full Text]
17. Golenbock, D. T., Y. Liu, F. H. Millham, M. W. Freeman, R. A. Zoeller. 1993. Surface expression of human CD14 in Chinese hamster ovary fibroblasts imparts macrophage-like responsiveness to bacterial endotoxin. J. Biol. Chem. 268:22055.[Abstract/Free Full Text]
18. Libby, P., G. Sukhova, R. T. Lee, Z. S. Galis. 1995. Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. J. Cardiovasc. Pharmacol. 25:(Suppl. 2):S9.
19. Jindal, S., E. Burke, B. Bettencourt, S. Khandekar, R. A. Young, D. S. Dwyer. 1994. Human Hsp60: bacterial expression, purification, development of monoclonal antibodies and a sandwich ELISA for quantitation. Immunol. Lett. 39:127.[Medline]
20. Cavaillon, J. M., N. Haeffner-Cavaillon. 1986. Polymyxin-B inhibition of LPS-induced interleukin-1 secretion by human monocytes is dependent upon the LPS origin. Mol. Immunol. 23:965.[Medline]
21. Frey, E. A., D. S. Miller, T. G. Jahr, A. Sundan, V. Bazil, T. Espevik, B. B. Finlay, S. D. Wright. 1992. Soluble CD14 participates in the response of cells to lipopolysaccharide. J. Exp. Med. 176:1665.[Abstract/Free Full Text]
22. Raingeaud, J., S. Gupta, J. S. Rogers, M. Dickens, J. Han, R. J. Ulevitch, R. J. Davis. 1995. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J. Biol. Chem. 270:7420.[Abstract/Free Full Text]
23. Manthey, C. L., S. W. Wang, S. D. Kinney, Z. Yao. 1998. SB202190, a selective inhibitor of p38 mitogen-activated protein kinase, is a powerful regulator of LPS-induced mRNAs in monocytes. J. Leukocyte Biol. 64:409.[Abstract]
24. Tabona, P., K. Reddi, S. Khan, S. P. Nair, S. J. Crean, S. Meghji, M. Wilson, M. Preuss, A. D. Miller, S. Poole, S. Carne, B. Henderson. 1998. Homogeneous Escherichia coli chaperonin 60 induces IL-1ß and IL-6 gene expression in human monocytes by a mechanism independent of protein conformation. J. Immunol. 161:1414.[Abstract/Free Full Text]
25. Retzlaff, C., Y. Yamamoto, P. S. Hoffman, H. Friedman, T. W. Klein. 1994. Bacterial heat shock proteins directly induce cytokine mRNA and interleukin-1 secretion in macrophage cultures. Infect Immun. 62:5689.[Abstract/Free Full Text]
26. Retzlaff, C., Y. Yamamoto, S. Okubo, P. S. Hoffman, H. Friedman, T. W. Klein. 1996. Legionella pneumophila heat-shock protein-induced increase of interleukin-1ß mRNA involves protein kinase C signalling in macrophages. Immunology 89:281.[Medline]
27. Chen, W., U. Syldath, K. Bellmann, V. Burkart, H. Kolb. 1999. Human 60-kDa heat-shock protein: a danger signal to the innate immune system. J. Immunol. 162:3212.[Abstract/Free Full Text]
28. Zhang, Y., M. Doerfler, T. C. Lee, B. Guillemin, W. N. Rom. 1993. Mechanisms of stimulation of interleukin-1ß and tumor necrosis factor- by Mycobacterium tuberculosis components. J. Clin. Invest. 91:2076.
29. Fenton, M. J., D. T. Golenbock. 1998. LPS-binding proteins and receptors. J. Leukocyte Biol. 64:25.[Abstract]
30. Rock, F. L., G. Hardiman, J. C. Timans, R. A. Kastelein, J. F. Bazan. 1998. A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. USA 95:588.[Abstract/Free Full Text]
31. Chow, J. C., D. W. Young, D. T. Golenbock, W. J. Christ, F. Gusovsky. 1999. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J. Biol. Chem. 274:10689.[Abstract/Free Full Text]
32. Heine, H., C. J. Kirschning, E. Lien, B. G. Monks, M. Rothe, D. T. Golenbock. 1999. Cutting edge: cells that carry a null allele for Toll-like receptor 2 are capable of responding to endotoxin. J. Immunol. 162:6971.[Abstract/Free Full Text]
33. Hoshino, K., O. Takeuchi, T. Kawai, H. Sanjo, T. Ogawa, Y. Takeda, K. Takeda, S. Akira. 1999. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the LPS gene product. J. Immunol. 162:3749.[Abstract/Free Full Text]
34. Qureshi, S. T., L. Larivire, G. Leveque, S. Clermont, K. J. Moore, P. Gros, D. Malo. 1999. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J. Exp. Med. 189:615.[Abstract/Free Full Text]
35. Yoshimura, A., E. Lien, R. R. Ingalls, E. Tuomanen, R. Dziarski, D. Golenbock. 1999. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 163:1.[Abstract/Free Full Text]
36. Young, R. A., T. J. Elliot. 1989. Stress proteins, infection and immune surveillance. Cell 59:5.[Medline]
37. Libby, P.. 1995. Molecular bases of the acute coronary syndromes. Circulation 91:2844.[Free Full Text]
38. Libby, P., D. Egan, S. Skarlatos. 1997. Role of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research. Circulation 96:4095.[Free Full Text]
39. Kol, A., P. Libby. 1998. The mechanisms by which infectious agents may contribute to atherosclerosis and its clinical manifestations. Trends Cardiovasc. Med. 8:191.[Medline]
40. Geng, Y. J.. 1997. Regulation of programmed cell death or apoptosis in atherosclerosis. Heart Vessels (Suppl. 12):76.
41. Schett, G., B. Metzler, R. Kleindienst, A. Amberger, H. Recheis, Q. Xu, G. Wick. 1999. Myocardial injury leads to a release of heat shock protein (hsp) 60 and a suppression of the anti-hsp65 immune response. Cardiovasc. Res. 42:685.[Abstract/Free Full Text]
42. Xu, Q., H. Dietrich, H. J. Steiner, A. M. Gown, B. Schoel, G. Mikuz, S. H. Kaufmann, G. Wick. 1992. Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65. Arterioscler. Thromb. 12:789.[Abstract/Free Full Text]
43. Wick, G., R. Kleindienst, G. Schett, A. Amberger, Q. Xu. 1995. Role of heat shock protein 65/60 in the pathogenesis of atherosclerosis. Int. Arch. Allergy Immunol. 107:130.[Medline]

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				T. Chen, J. Guo, C. Han, M. Yang, and X. Cao Heat Shock Protein 70, Released from Heat-Stressed Tumor Cells, Initiates Antitumor Immunity by Inducing Tumor Cell Chemokine Production and Activating Dendritic Cells via TLR4 Pathway J. Immunol., February 1, 2009; 182(3): 1449 - 1459. [Abstract] [Full Text] [PDF]

				F. N. Wuppermann, K. Molleken, M. Julien, C. A. Jantos, and J. H. Hegemann Chlamydia pneumoniae GroEL1 Protein Is Cell Surface Associated and Required for Infection of HEp-2 Cells J. Bacteriol., May 15, 2008; 190(10): 3757 - 3767. [Abstract] [Full Text] [PDF]

				A. Osterloh, A. Veit, A. Gessner, B. Fleischer, and M. Breloer Hsp60-mediated T cell stimulation is independent of TLR4 and IL-12 Int. Immunol., March 1, 2008; 20(3): 433 - 443. [Abstract] [Full Text] [PDF]

				A. Nareika, Y.-B. Im, B. A Game, E. H Slate, J. J Sanders, S. D London, M. F Lopes-Virella, and Y. Huang High glucose enhances lipopolysaccharide-stimulated CD14 expression in U937 mononuclear cells by increasing nuclear factor {kappa}B and AP-1 activities J. Endocrinol., January 1, 2008; 196(1): 45 - 55. [Abstract] [Full Text] [PDF]

				S. Kettner, F. Kalthoff, P. Graf, E. Priller, F. Kricek, I. Lindley, and T. Schweighoffer EWI-2/CD316 Is an Inducible Receptor of HSPA8 on Human Dendritic Cells Mol. Cell. Biol., November 1, 2007; 27(21): 7718 - 7726. [Abstract] [Full Text] [PDF]

				R. W. LaRue, B. D. Dill, D. K. Giles, J. D. Whittimore, and J. E. Raulston Chlamydial Hsp60-2 Is Iron Responsive in Chlamydia trachomatis Serovar E-Infected Human Endometrial Epithelial Cells In Vitro Infect. Immun., May 1, 2007; 75(5): 2374 - 2380. [Abstract] [Full Text] [PDF]

				A. Osterloh, U. Kalinke, S. Weiss, B. Fleischer, and M. Breloer Synergistic and Differential Modulation of Immune Responses by Hsp60 and Lipopolysaccharide J. Biol. Chem., February 16, 2007; 282(7): 4669 - 4680. [Abstract] [Full Text] [PDF]

				F. Cao, A. Castrillo, P. Tontonoz, F. Re, and G. I. Byrne Chlamydia pneumoniae-Induced Macrophage Foam Cell Formation Is Mediated by Toll-Like Receptor 2 Infect. Immun., February 1, 2007; 75(2): 753 - 759. [Abstract] [Full Text] [PDF]

				J. P. Mackern-Oberti, M. Maccioni, C. Cuffini, G. Gatti, and V. E. Rivero Susceptibility of Prostate Epithelial Cells to Chlamydia muridarum Infection and Their Role in Innate Immunity by Recruitment of Intracellular Toll-Like Receptors 4 and 2 and MyD88 to the Inclusion Infect. Immun., December 1, 2006; 74(12): 6973 - 6981. [Abstract] [Full Text] [PDF]

				R. Aneja, K. Odoms, K. Dunsmore, T. P. Shanley, and H. R. Wong Extracellular Heat Shock Protein-70 Induces Endotoxin Tolerance in THP-1 Cells J. Immunol., November 15, 2006; 177(10): 7184 - 7192. [Abstract] [Full Text] [PDF]

				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]

				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]

				G. E. Bergonzelli, D. Granato, R. D. Pridmore, L. F. Marvin-Guy, D. Donnicola, and I. E. Corthesy-Theulaz GroEL of Lactobacillus johnsonii La1 (NCC 533) Is Cell Surface Associated: Potential Role in Interactions with the Host and the Gastric Pathogen Helicobacter pylori Infect. Immun., January 1, 2006; 74(1): 425 - 434. [Abstract] [Full Text] [PDF]

				S. G. Elner, H. R. Petty, V. M. Elner, A. Yoshida, Z.-M. Bian, D. Yang, and A. L. Kindzelskii TLR4 Mediates Human Retinal Pigment Epithelial Endotoxin Binding and Cytokine Expression Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4627 - 4633. [Abstract] [Full Text] [PDF]

				J. P.J. Halcox, J. Deanfield, A. Shamaei-Tousi, B. Henderson, A. Steptoe, A. R.M. Coates, A. Singhal, and A. Lucas Circulating Human Heat Shock Protein 60 in the Blood of Healthy Teenagers: A Novel Determinant of Endothelial Dysfunction and Early Vascular Injury? Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): e141 - e142. [Full Text] [PDF]

				V. C. Mehra, V. S. Ramgolam, and J. R. Bender Cytokines and cardiovascular disease J. Leukoc. Biol., October 1, 2005; 78(4): 805 - 818. [Abstract] [Full Text] [PDF]

				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]

				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]

				M. W. Graner and D. D. Bigner Chaperone proteins and brain tumors: Potential targets and possible therapeutics Neuro-oncol, July 1, 2005; 7(3): 260 - 278. [Abstract] [PDF]

				K. Yaraei, L. A. Campbell, X. Zhu, W. C. Liles, C.-c. Kuo, and M. E. Rosenfeld Effect of Chlamydia pneumoniae on Cellular ATP Content in Mouse Macrophages: Role of Toll-Like Receptor 2 Infect. Immun., July 1, 2005; 73(7): 4323 - 4326. [Abstract] [Full Text] [PDF]

				G. I. Lancaster and M. A. Febbraio Exosome-dependent Trafficking of HSP70: A NOVEL SECRETORY PATHWAY FOR CELLULAR STRESS PROTEINS J. Biol. Chem., June 17, 2005; 280(24): 23349 - 23355. [Abstract] [Full Text] [PDF]

				G. Pfister, C. M. Stroh, H. Perschinka, M. Kind, M. Knoflach, P. Hinterdorfer, and G. Wick Detection of HSP60 on the membrane surface of stressed human endothelial cells by atomic force and confocal microscopy J. Cell Sci., April 15, 2005; 118(8): 1587 - 1594. [Abstract] [Full Text] [PDF]

				P. Tormay, A. R. M. Coates, and B. Henderson The Intercellular Signaling Activity of the Mycobacterium tuberculosis Chaperonin 60.1 Protein Resides in the Equatorial Domain J. Biol. Chem., April 8, 2005; 280(14): 14272 - 14277. [Abstract] [Full Text] [PDF]

				Y. Wang, T. Whittall, E. McGowan, J. Younson, C. Kelly, L. A. Bergmeier, M. Singh, and T. Lehner Identification of Stimulating and Inhibitory Epitopes within the Heat Shock Protein 70 Molecule That Modulate Cytokine Production and Maturation of Dendritic Cells J. Immunol., March 15, 2005; 174(6): 3306 - 3316. [Abstract] [Full Text] [PDF]

				A. Lang, D. Benke, F. Eitner, D. Engel, S. Ehrlich, M. Breloer, E. Hamilton-Williams, S. Specht, A. Hoerauf, J. Floege, et al. Heat Shock Protein 60 Is Released in Immune-Mediated Glomerulonephritis and Aggravates Disease: In Vivo Evidence for an Immunologic Danger Signal J. Am. Soc. Nephrol., February 1, 2005; 16(2): 383 - 391. [Abstract] [Full Text] [PDF]

				B. Berwin, Y. Delneste, R. V. Lovingood, S. R. Post, and S. V. Pizzo SREC-I, a Type F Scavenger Receptor, Is an Endocytic Receptor for Calreticulin J. Biol. Chem., December 3, 2004; 279(49): 51250 - 51257. [Abstract] [Full Text] [PDF]

				I. H Haralambieva, I. D Iankov, P. V Ivanova, V. Mitev, and I. G Mitov Chlamydophila pneumoniae induces p44/p42 mitogen-activated protein kinase activation in human fibroblasts through Toll-like receptor 4 J. Med. Microbiol., December 1, 2004; 53(12): 1187 - 1193. [Abstract] [Full Text] [PDF]

				L. L. Stoll, G. M. Denning, and N. L. Weintraub Potential Role of Endotoxin as a Proinflammatory Mediator of Atherosclerosis Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2227 - 2236. [Abstract] [Full Text] [PDF]

				A. Osterloh, F. Meier-Stiegen, A. Veit, B. Fleischer, A. von Bonin, and M. Breloer Lipopolysaccharide-free Heat Shock Protein 60 Activates T Cells J. Biol. Chem., November 12, 2004; 279(46): 47906 - 47911. [Abstract] [Full Text] [PDF]

				R Arroyo-Espliguero, P Avanzas, S Jeffery, and J C Kaski CD14 and toll-like receptor 4: a link between infection and acute coronary events? Heart, September 1, 2004; 90(9): 983 - 988. [Abstract] [Full Text] [PDF]

				M.-F. Tsan and B. Gao Endogenous ligands of Toll-like receptors J. Leukoc. Biol., September 1, 2004; 76(3): 514 - 519. [Abstract] [Full Text] [PDF]

				M. G. Hartley, M. Green, G. Choules, D. Rogers, D. G. C. Rees, S. Newstead, A. Sjostedt, and R. W. Titball Protection Afforded by Heat Shock Protein 60 from Francisella tularensis Is Due to Copurified Lipopolysaccharide Infect. Immun., July 1, 2004; 72(7): 4109 - 4113. [Abstract] [Full Text] [PDF]

				M. Fleshner and M. L. Laudenslager Psychoneuroimmunology: Then and Now Behav Cogn Neurosci Rev, June 1, 2004; 3(2): 114 - 130. [Abstract] [PDF]

				M.-F. Tsan and B. Gao Cytokine function of heat shock proteins Am J Physiol Cell Physiol, April 1, 2004; 286(4): C739 - C744. [Abstract] [Full Text] [PDF]

				S. Bas, B. R. Gauthier, U. Spenato, S. Stingelin, and C. Gabay CD14 Is an Acute-Phase Protein J. Immunol., April 1, 2004; 172(7): 4470 - 4479. [Abstract] [Full Text] [PDF]

				J. L. Wampler, K.-P. Kim, Z. Jaradat, and A. K. Bhunia Heat Shock Protein 60 Acts as a Receptor for the Listeria Adhesion Protein in Caco-2 Cells Infect. Immun., February 1, 2004; 72(2): 931 - 936. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				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]

				B. OSTERUD and E. BJORKLID Role of Monocytes in Atherogenesis Physiol Rev, October 1, 2003; 83(4): 1069 - 1112. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				J. P. Higgins Chlamydia pneumoniae and Coronary Artery Disease: The Antibiotic Trials Mayo Clin. Proc., March 1, 2003; 78(3): 321 - 332. [Abstract] [PDF]

				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]

				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]

				J. Campisi and M. Fleshner Role of extracellular HSP72 in acute stress-induced potentiation of innate immunity in active rats J Appl Physiol, January 1, 2003; 94(1): 43 - 52. [Abstract] [Full Text] [PDF]

				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]

				J. C. Baker-LePain, M. Sarzotti, T. A. Fields, C.-Y. Li, and C. V. Nicchitta GRP94 (gp96) and GRP94 N-Terminal Geldanamycin Binding Domain Elicit Tissue Nonrestricted Tumor Suppression J. Exp. Med., December 2, 2002; 196(11): 1447 - 1459. [Abstract] [Full Text] [PDF]

				K. Bethke, F. Staib, M. Distler, U. Schmitt, H. Jonuleit, A. H. Enk, P. R. Galle, and M. Heike Different Efficiency of Heat Shock Proteins (HSP) to Activate Human Monocytes and Dendritic Cells: Superiority of HSP60 J. Immunol., December 1, 2002; 169(11): 6141 - 6148. [Abstract] [Full Text] [PDF]

				E. Noessner, R. Gastpar, V. Milani, A. Brandl, P. J. S. Hutzler, M. C. Kuppner, M. Roos, E. Kremmer, A. Asea, S. K. Calderwood, et al. Tumor-Derived Heat Shock Protein 70 Peptide Complexes Are Cross-Presented by Human Dendritic Cells J. Immunol., November 15, 2002; 169(10): 5424 - 5432. [Abstract] [Full Text] [PDF]

				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]

				A. Shor, P. Libby, P. M. Ridker, and A. Maseri Atherosclerosis: Lipid Infiltration or Chlamydia pneumoniae Infection? * Response Circulation, October 29, 2002; 106 (18): e135 - e136. [Full Text] [PDF]

				Q. Xu Role of Heat Shock Proteins in Atherosclerosis Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1547 - 1559. [Abstract] [Full Text] [PDF]

				B. Billack, D. E. Heck, T. M. Mariano, C. R. Gardner, R. Sur, D. L. Laskin, and J. D. Laskin Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and endothelial cells Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1267 - C1277. [Abstract] [Full Text] [PDF]

				T. Becker, F.-U. Hartl, and F. Wieland CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes J. Cell Biol., September 29, 2002; 158(7): 1277 - 1285. [Abstract] [Full Text] [PDF]

				R. Maron, G. Sukhova, A.-M. Faria, E. Hoffmann, F. Mach, P. Libby, and H. L. Weiner Mucosal Administration of Heat Shock Protein-65 Decreases Atherosclerosis and Inflammation in Aortic Arch of Low-Density Lipoprotein Receptor-Deficient Mice Circulation, September 24, 2002; 106(13): 1708 - 1715. [Abstract] [Full Text] [PDF]

				G. K. Hansson, P. Libby, U. Schonbeck, and Z.-Q. Yan Innate and Adaptive Immunity in the Pathogenesis of Atherosclerosis Circ. Res., August 23, 2002; 91(4): 281 - 291. [Abstract] [Full Text] [PDF]

				J C Ranford and B Henderson Chaperonins in disease: mechanisms, models, and treatments Mol. Pathol., August 1, 2002; 55(4): 209 - 213. [Abstract] [Full Text] [PDF]

				W. Koenig, N. Khuseyinova, M. M. Hoffmann, W. Marz, M. Frohlich, A. Hoffmeister, H. Brenner, and D. Rothenbacher CD14 C(-260)->T polymorphism, plasma levels of the soluble endotoxin receptor CD14, their association with chronic infections and risk of stable coronary artery disease J. Am. Coll. Cardiol., July 3, 2002; 40(1): 34 - 42. [Abstract] [Full Text] [PDF]

				G. S. Deepe, Jr., and R. S. Gibbons Cellular and Molecular Regulation of Vaccination with Heat Shock Protein 60 from Histoplasma capsulatum Infect. Immun., July 1, 2002; 70(7): 3759 - 3767. [Abstract] [Full Text] [PDF]

				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]

				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]

				H. O. Barazi, L. Zhou, N. S. Templeton, H. C. Krutzsch, and D. D. Roberts Identification of Heat Shock Protein 60 as a Molecular Mediator of {alpha}3{beta}1 Integrin Activation Cancer Res., March 1, 2002; 62(5): 1541 - 1548. [Abstract] [Full Text] [PDF]

				A. G. Pockley Heat Shock Proteins, Inflammation, and Cardiovascular Disease Circulation, February 26, 2002; 105(8): 1012 - 1017. [Full Text] [PDF]

				Y. Bulut, E. Faure, L. Thomas, H. Karahashi, K. S. Michelsen, O. Equils, S. G. Morrison, R. P. Morrison, and M. Arditi Chlamydial Heat Shock Protein 60 Activates Macrophages and Endothelial Cells Through Toll-Like Receptor 4 and MD2 in a MyD88-Dependent Pathway J. Immunol., February 1, 2002; 168(3): 1435 - 1440. [Abstract] [Full Text] [PDF]

				C. Habich, K. Baumgart, H. Kolb, and V. Burkart The Receptor for Heat Shock Protein 60 on Macrophages Is Saturable, Specific, and Distinct from Receptors for Other Heat Shock Proteins J. Immunol., January 15, 2002; 168(2): 569 - 576. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				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]

				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]

				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]

				B. C. Berk Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms Physiol Rev, July 1, 2001; 81(3): 999 - 1030. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				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]

				J S H Gaston Immunological basis of chlamydia induced reactive arthritis Sex Transm Inf, June 1, 2000; 76(3): 156 - 161. [Full Text] [PDF]

				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]

				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]

				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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