Early events in the recognition of danger signals after tissue injury

Journal of Leukocyte Biology

Volumn 83, Issue 3, 2008, Pages 546-552

  Kaczorowski, David J ^a   Mollen, Kevin P ^a   Edmonds, Rebecca ^a   Billiar, Timothy R ^a,b  

^a UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^b PRESBYTERIAN UNIVERSITY HOSPITAL   (United States)

Author keywords

HMGB1; Inflammation; Toll like receptors; Trauma

Indexed keywords

HEPARAN SULFATE; HIGH MOBILITY GROUP B1 PROTEIN; HYALURONIC ACID; NEUTRALIZING ANTIBODY; TOLL LIKE RECEPTOR 4; LIPOPOLYSACCHARIDE; TLR4 PROTEIN, HUMAN; TOLL LIKE RECEPTOR;

CONFERENCE PAPER; FEMUR FRACTURE; HEMORRHAGIC SHOCK; HUMAN; IMMUNE RESPONSE; INFLAMMATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TISSUE INJURY; BIOLOGICAL MODEL; INJURY; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; WOUND HEALING;

FEMORAL FRACTURES; HUMANS; INFLAMMATION; LIPOPOLYSACCHARIDES; MODELS, BIOLOGICAL; TOLL-LIKE RECEPTOR 4; TOLL-LIKE RECEPTORS; WOUND HEALING; WOUNDS AND INJURIES;

EID: 43349094278     PISSN: 07415400     EISSN: None     Source Type: Journal    
DOI: 10.1189/jlb.0607374     Document Type: Conference Paper

References (89)

1. Kapetanovic, R., Cavaillon, J. M. (2007) Early events in innate immunity in the recognition of microbial pathogens. Expert Opin. Biol. Ther. 7, 907-918.
2. Akira, S., Uematsu, S., Takeuchi, O. (2006) Pathogen recognition and innate immunity. Cell 124, 783-801.
3. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M., Hoffmann, J. A. (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973-983.
4. Medzhitov, R., Preston-Hurlburt, P., Janeway Jr., C. A. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397.
5. Kirk, P., Bazan, J. F. (2005) Pathogen recognition: TLRs throw us a curve. Immunity 23, 347-350.
6. Bell, J. K., Mullen, G. E., Leifer, C. A., Mazzoni, A., Davies, D. R., Segal, D. M. (2003) Leucine-rich repeats and pathogen recognition in Toll-like receptors. Trends Immunol. 24, 528-533.
7. Means, T. K., Golenbock, D. T., Fenton, M. J. (2000) Structure and function of Toll-like receptor proteins. Life Sci. 68, 241-258.
8. Kawai, T., Akira, S. (2006) TLR signaling. Cell Death Differ. 13, 816-825.
9. Muzio, M., Bosisio, D., Polentarutti, N., D'amico, G., Stoppacciaro, A., Mancinelli, R., van't Veer, C., Penton-Rol, G., Ruco, L. P., Allavena, P., Mantovani, A. (2000) Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J. Immunol. 164, 5998-6004.
10. Kabelitz, D. (2007) Expression and function of Toll-like receptors in T lymphocytes. Curr. Opin. Immunol. 19, 39-45.
11. Triantafilou, K., Triantafilou, M., Mouratis, M., Gamper, F. (2007) Stoichiometry of Toll-like receptor 4 within the LPS-sensing apparatus. Inflamm. Res. 56, S121.
12. Latz, E. (2007) TLR9 is activated by multiple conformational changes. Inflamm. Res. 56, S114.
13. O'Neill, L. A. J., Bowie, A. G. (2007) The family of five: TIR-domain-containing adaptors in Toll-like receptor signaling. Nat. Rev. Immunol. 7, 353-364.
14. Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C., Ghosh, S., Janeway Jr., C. A. (1998) MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol. Cell 2, 253-258.
15. Suzuki, S., Kelley, R. E., Dandapani, B. K., Reyes-Iglesias, Y., Dietrich, W. D., Duncan, R. C. (2002) Severe impairment of interleukin-1 and Toll-like receptor signaling in mice lacking IRAK-4. Nature 416, 750-756.
16. Kawagoe, T., Sato, S., Jung, A., Yamamoto, M., Matsui, K., Kato, H., Uematsu, S., Takeuchi, O., Akira, S. (2007) Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor-mediated immune responses but not in TCR signaling. J. Exp. Med. 204, 1013-1024.
17. Fitzgerald, K. A., Palsson-McDermott, E. M., Bowie, A. G., Jefferies, C. A., Mansell, A. S., Brady, G., Brint, E., Dunne, A., Gray, P., Harte, M. T., McMurray, D., Smith, D. E., Sims, J. E., Bird, T. A., O'Neill, L. A. (2001) Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413, 78-83.
18. Mansell, A., Brint, E., Gould, J. A., O'Neill, L. A., Hertzog, P. J. (2004) Mal interacts with tumor necrosis factor receptor-associated factor (TRAF)-6 to mediate NF-κB activation by Toll-like receptor (TLR)-2 and TLR4. J. Biol. Chem. 279, 37227-37230.
19. Gohda, J., Matsumura, T., Inoue, J. (2004) Cutting edge: TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF)-dependent pathway in TLR signaling. J. Immunol. 173, 2913-2917.
20. Qian, Y., Commane, M., Ninomiya-Tsuji, J., Matsumoto, K., Li, X. (2001) IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFκ B. J. Biol. Chem. 276, 41661-41667.
21. Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J., Chen, Z. J. (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-351.
22. Burns, K., Janssens, S., Brissoni, B., Olivos, N., Beyaert, R., Tschopp, J. (2003) Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J. Exp. Med. 197, 263-268.
23. Janssens, S., Burns, K., Vercammen, E., Tschopp, J., Beyaert, R. (2003) MyD88S, a splice variant of MyD88, differentially modulates NF-κB- and AP-1-dependent gene expression. FEBS Lett. 548, 103-107.
24. Kobayashi, K., Hernandez, L. D., Galan, J. E., Janeway Jr., C. A., Medzhitov, R., Flavell, R. A. (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110, 191-202.
25. Gray, P., Dunne, A., Brikos, C., Jefferies, C. A., Doyle, S. L., O'Neill, L. A. (2006) MyD88 adapter-like (Mal) is phosphorylated by Bruton's tyrosine kinase during TLR2 and TLR4 signal transduction. J. Biol. Chem. 281, 10489-10495.
26. Mansell, A., Smith, R., Doyle, S. L., Gray, P., Fenner, J. E., Crack, P. J., Nicholson, S. E., Hilton, D. J., O'Neill, L. A., Hertzog, P. J. (2006) Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat. Immunol. 7, 148-155.
27. Yamamoto, M., Sato, S., Mori, K., Hoshino, K., Takeuchi, O., Takeda, K., Akira, S. (2002) Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-β promoter in the Toll-like receptor signaling. J. Immunol. 169, 6668-6672.
28. Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K., Akira, S. (2003) Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway. Science 301, 640-643.
29. McGettrick, A. F., Brint, E. K., Palsson-McDermott, E. M., Rowe, D. C., Golenbock, D. T., Gay, N. J., Fitzgerald, K. A., O'Neill, L. A. (2006) Trif-related adapter molecule is phosphorylated by PKC{ε} during Toll-like receptor 4 signaling. Proc. Natl. Acad. Sci. USA 103, 9196-9201.
30. Oganesyan, G., Saha, S. K., Guo, B., He, J. Q., Shahangian, A., Zarnegar, B., Perry, A., Cheng, G. (2006) Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439, 208-211.
31. Sato, S., Sugiyama, M., Yamamoto, M., Watanabe, Y., Kawai, T., Takeda, K., Akira, S. (2003) Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-κ B and IFN-regulatory factor-3, in the Toll-like receptor signaling. J. Immunol. 171, 4304-4310.
32. Ruckdeschel, K., Pfaffinger, G., Haase, R., Sing, A., Weighardt, H., Häcker, G., Holzmann, B., Heesemann, J. (2004) Signaling of apoptosis through TLRs critically involves Toll/IL-1 receptor domain-containing adapter inducing IFN-β, but not MyD88, in bacteria-infected murine macrophages. J. Immunol. 173, 3320-3328.
33. Carty, M., Goodbody, R., Schroder, M., Stack, J., Moynagh, P. N., Bowie, A. G. (2006) The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat. Immunol. 7, 1074-1081.
34. Poltorak, A., He, X., Smirnova, I., Liu, M. Y., Van Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B., Beutler, B. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085-2088.
35. Tobias, P. S., Soldau, K., Ulevitch, R. J. (1986) Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J. Exp. Med. 164, 777-793.
36. Wright, S. D., Ramos, R. A., Tobias, P. S., Ulevitch, R. J., Mathison, J. C. (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249, 1431-1433.
37. Bazil, V., Baudys, M., Hilgert, I., Stefanová, I., Low, M. G., Zbrozek, J., Horejsí, V. (1989) Structural relationship between the soluble and membrane-bound forms of human monocyte surface glycoprotein CD14. Mol. Immunol. 26, 657-662.
38. Haziot, A., Chen, S., Ferrero, E., Low, M. G., Silber, R., Goyert, S. M. (1988) The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J. Immunol. 141, 547-552.
39. Brunn, G., Platt, J. (2007) Endogenous controls of Toll-like receptor 4 signaling. Inflamm. Res. 56, S109.
40. McSwiney, E., Wang, J. H., Redmond, H. P. (2007) Phosphoinositide 3-kinase inhibition negatively regulates both TLR2- and TLR4-mediated proinflammatory responses in murine peritoneal macrophages. Inflamm. Res. 56, S119.
41. Miyake, K. (2007) Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin. Immunol. 19, 3-10.
42. Oyama, J., Blais Jr., C., Liu, X., Pu, M., Kobzik, L., Kelly, R. A., Bourcier, T. (2004) Reduced myocardial ischemia-reperfusion injury in Toll-like receptor 4-deficient mice. Circulation 109, 784-789.
43. Tsung, A., Hoffman, R. A., Izuishi, K., Critchlow, N. D., Nakao, A., Chan, M. H., Lotze, M. T., Geller, D. A., Billiar, T. R. (2005) Hepatic ischemia/reperfusion injury involves functional TLR4 signaling in nonparenchymal cells. J. Immunol. 175, 7661-7668.
44. Kaczorowski, D. J., Nakao, A., Mollen, K. P., Murase, N., Billiar, T. R. (2007) Toll-like receptor 4 (TLR4) mediates systemic inflammation after cardiac transplantation. Inflamm. Res. 56, S121.
45. DeMaria, E. J., Pellicane, J. V., Lee, R. B. (1993) Hemorrhagic shock in endotoxin-resistant mice: improved survival unrelated to deficient production of tumor necrosis factor. J. Trauma 35, 720-724.
46. Prince, J. M., Levy, R. M., Yang, R., Mollen, K. P., Fink, M. P., Vodovotz, Y., Billiar, T. R. (2006) Toll-like receptor-4 signaling mediates hepatic injury and systemic inflammation in hemorrhagic shock. J. Am. Coll. Surg. 202, 407-417.
47. Billiar, T. R. (2007) Early events in the host recognition of endogenous danger signal. Symposium 78. 7th World Congress on Trauma, Shock, Inflammation, and Sepsis, Munich, Germany.
48. Barsness, K. A., Arcaroli, J., Harken, A. H., Abraham, E., Banerjee, A., Reznikov, L., McIntyre, R. C. (2004) Hemorrhage-induced acute lung injury is TLR-4 dependent. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287, R592-R599.
49. Fan, J., Kapus, A., Marsden, P. A., Li, Y. H., Oreopoulos, G., Marshall, J. C., Frantz, S., Kelly, R. A., Medzhitov, R., Rotstein, O. D. (2002) Regulation of Toll-like receptor 4 expression in the lung following hemorrhagic shock and lipopolysaccharide. J. Immunol. 168, 5252-5259.
50. Powers, K. A., Szászi, K., Khadaroo, R. G., Tawadros, P. S., Marshall, J. C., Kapus, A., Rotstein, O. D. (2006) Oxidative stress generated by hemorrhagic shock recruits Toll-like receptor 4 to the plasma membrane in macrophages. J. Exp. Med. 203, 1951-1961.
51. Levy, R. M., Prince, J. M., Yang, R., Mollen, K. P., Liao, H., Watson, G. A., Fink, M. P., Vodovotz, Y., Billiar, T. R. (2006) Systemic inflammation and remote organ damage following bilateral femur fracture requires Toll-like receptor 4. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R970-R976.
52. Billiar, T. R. (2007) TLR4 signaling is required for the systemic inflammatory response following femur fracture. Symposium 329. 7th World Congress on Trauma, Shock, Inflammation, and Sepsis, Munich, Germany.
53. Wang, H., Bloom, O., Zhang, M., Vishnubhakat, J. M., Ombrellino, M., Che, J., Frazier, A., Yang, H., Ivanova, S., Borovikova, L., Manogue, K. R., Faist, E., Abraham, E., Andersson, J., Andersson, U., Molina, P. E., Abumrad, N. N., Sama, A., Tracey, K. J. (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248-251.
54. Yang, R., Harada, T., Mollen, K. P., Prince, J. M., Levy, R. M., Englert, J. A., Gallowitsch-Puerta, M., Yang, L., Yang, H., Tracey, K. J., Harbrecht, B. G., Billiar, T. R., Fink, M. P. (2006) Anti-HMGB1 neutralizing antibody ameliorates gut barrier dysfunction and improves survival after hemorrhagic shock. Mol. Med. 12, 105-114.
55. Levy, R. M., Mollen, K. P., Prince, J. M., Kaczorowski, D. J., Vallabhaneni, R., Liu, S., Tracey, K. J., Lotze, M. T., Hackam, D. J., Fink, M. P., Vodovotz, Y., Billiar, T. R. (2007) Systemic inflammation and remote organ injury following trauma require HMGB1. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R1538-R1544.
56. Platt, J., Brunn, G., Johnson, G. (2007) Weighing exogenous versus endogenous triggers of SIRS. Inflamm. Res. 56, 109.
57. Platt, J. (2007) Heparan sulfate and the initiation of systemic inflammation. Inflamm. Res. 56, S77.
58. Johnson, G. B., Brunn, G. J., Kodaira, Y., Platt, J. L. (2002) Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J. Immunol. 168, 5233-5239.
59. Johnson, G. B., Brunn, G. J., Platt, J. L. (2004) Cutting edge: an endogenous pathway to systemic inflammatory response syndrome (SIRS)-like reactions through Toll-like receptor 4. J. Immunol. 172, 20-24.
60. Termeer, C., Benedix, F., Sleeman, J., Fieber, C., Voith, U., Ahrens, T., Miyake, K., Freudenberg, M., Galanos, C., Simon, J. C. (2002) Oligosaccharides of Hyaluronan activate dendritic cells via Toll-like receptor 4. J. Exp. Med. 195, 99-111.
61. Taylor, K. R., Trowbridge, J. M., Rudisill, J. A., Termeer, C. C., Simon, J. C., Gallo, R. L. (2004) Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J. Biol. Chem. 279, 17079-17084.
62. Taylor, K. R., Yamasaki, K., Radek, K. A., Di Nardo, A., Goodarzi, H., Golenbock, D., Beutler, B., Gallo, R. L. (2007) Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2. J. Biol. Chem. 282, 18265-18275.
63. Smiley, S. T., King, J. A., Hancock, W. W. (2001) Fibrinogen stimulates macrophage chemokine secretion through Toll-like receptor 4. J. Immunol. 167, 2887-2894.
64. Kim, S., Kim, S., Gupta, S., Knowlton, A. (2007) HSP60 release after LPS treatment and its effects on cardiac myocytes. Inflamm. Res. 56, S149.
65. Multhoff, G., Gerhmann, M. (2007) HSP70 export from tumor cells - a danger signal for the immune system. Inflamm. Res. 56, S149.
66. Williams, J. H. (2007) Heat shock proteins as danger signals. Inflamm. Res. 56, S327.
67. Ohashi, K., Burkart, V., Flohe, S., Kolb, H. (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor-4 complex. J. Immunol. 164, 558-561.
68. Maguire, M., Poole, S., Coates, A. R., Tormay, P., Wheeler-Jones, C., Henderson, B. (2005) Comparative cell signaling activity of ultrapure recombinant chaperonin 60 proteins from prokaryotes and eukaryotes. Immunology 115, 231-238.
69. Warger, T., Hilf, N., Rechtsteiner, G., Haselmayer, P., Carrick, D. M., Jonuleit, H., von Landenberg, P., Rammensee, H. G., Nicchitta, C. V., Radsak, M. P., Schild, H. (2006) Interaction of TLR2 and TLR4 ligands with the N-terminal domain of Gp96 amplifies innate and adaptive immune responses. J. Biol. Chem. 281, 22545-22553.
70. Vogl, T., Tenbrock, K., Van Zeolen, M. A., Ehrhardt, C., Ludwig, S., Roth, J. (2007) MRP8 and MRP14 are novel endogenous ligands of Toll-like receptor 4 and promote lethal endotoxin-induced shock. Inflamm. Res. 56, S115.
71. Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A., Nacken, W., Foell, D., van der Poll, T., Sorg, C., Roth, J. (2007) Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat. Med. 13, 1042-1049.
72. Schroeder, J. (2007) Psoriasin and the S-100 family of proteins: their role as defensins and alarmins. Inflamm. Res. 56, S70.
73. Rock, K., Shi, Y., Chen, C., Hearn, A. (2007) Uric acid as a danger signal with adjuvant properties. Inflamm. Res. 56, S76.
74. Tang, D., Shi, Y., Kang, R., Li, T., Xiao, W., Wang, H., Xiao, X. (2007) Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1. J. Leukoc. Biol. 81, 741-747.
75. Youn, J. H., Shin, J. S. (2006) Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretion. J. Immunol. 177, 7889-7897.
76. Yu, M., Wang, H., Ding, A., Golenbock, D. T., Latz, E., Czura, C. J., Fenton, M. J., Tracey, K. J., Yang, H. (2006) HMGB1 signals through Toll-like receptor (TLR) 4 and TLR2. Shock 26, 174-179.
77. Park, J. S., Gamboni-Robertson, F., He, Q., Svetkauskaite, D., Kim, J. Y., Strassheim, D., Sohn, J. W., Yamada, S., Maruyama, I., Banerjee, A., Ishizaka, A., Abraham, E. (2006) High mobility group box 1 protein interacts with multiple Toll-like receptors. Am. J. Physiol. Cell Physiol. 290, C917-C924.
78. Park, J. S., Svetkauskaite, D., He, Q., Kim, J. Y., Strassheim, D., Ishizaka, A., Abraham, E. (2004) Involvement of Toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J. Biol. Chem. 279, 7370-7377.
79. Mollen, K. P., Kaczorowski, D. J., Scott, M., Vallabhaneni, R., Billiar, T. R. (2007) High mobility group box 1 (HMGB1) induces Toll-like receptor 4 (TLR4) clustering within the lipid raft in macrophages. Inflamm. Res. 56, S116.
80. Martinon, F. (2007) The inflammasome: a danger signal sensing complex involved in autoinflammatory disease. Inflamm. Res. 56, S76.
81. Gaide, O., Watanabe, H., Petrilli, V., Contassot, E., Tschopp, J., French, L. (2007) Danger, NLRs, and delayed type hypersensitivity in the skin. Inflamm. Res. 56, S76.
82. Rock, K., Chen, C., Kono, H. (2007) Cell death and acute inflammation. Inflamm. Res. 56, S110.
83. Levi, M. (2007) The coagulation-inflammation connection in severe injury. Inflamm. Res. 56, S111.
84. Popovic, P., Matta, B., Prince, J., Ochoa, J. (2007) TLR4 signaling modulates arginase activity in myeloid suppressor cells after trauma. Inflamm. Res. 56, S81.
85. Walz, C., Zedler, S., Schneider, C. P., Bruns, C. J., Faist, E., Angele, M. K. (2007) Depressed T-cell function is responsible for prolonged immunosuppression following trauma-hemorrhage. Inflamm. Res. 56, S83.
86. Vodovotz, Y. (2007) Deciphering interactions among acute inflammation, tissue damage, and healing using mathematical models. Inflamm. Res. 56, S326.
87. Rossignol, D., Wittek, A., Lynn, M. (2007) Summary results of clinical trials of eritoran-a Toll-like receptor 4 antagonist. Inflamm. Res. 56, S125.
88. Rouhianinen, A., Rauvala, H. (2007) HMGB1 (Amphoterin) interactions with monocytes and platelets are inhibited by glycyrrhizin. Inflamm. Res. 56, S129.
89. Lorenzetto, C., Fumero, S., Barone, D., Traversa, S., Guyon, T., Borrelly, G. (2007) Use of single-point mutated HMGB1 box A variants as therapeutic agents in HMGB1 and RAGE related pathologies. Inflamm. Res. 56, A190.