Sterile inflammation: Sensing and reacting to damage

Nature Reviews Immunology

Volumn 10, Issue 12, 2010, Pages 826-837

  Chen, Grace Y ^a   Nuñez, Gabriel ^a  

^a UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CRYOPYRIN; CXCL2 CHEMOKINE; DOUBLE STRANDED DNA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLAMMASOME; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 33; LIPOPOLYSACCHARIDE; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN S 100; RETINOIC ACID INDUCIBLE PROTEIN I; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; URIC ACID;

CELL DEATH; CYTOKINE PRODUCTION; DROSOPHILA MELANOGASTER; EXTRACELLULAR MATRIX; HUMAN; INFLAMMATION; NONHUMAN; PATHOLOGY; PRIORITY JOURNAL; REVIEW; TISSUE INJURY; WOUND HEALING;

ANIMALS; CYTOKINES; DIABETES MELLITUS, TYPE 2; HUMANS; IMMUNITY, INNATE; INFLAMMATION; INFLAMMATION MEDIATORS; MICE; REACTIVE OXYGEN SPECIES; RECEPTORS, PATTERN RECOGNITION; REPERFUSION INJURY; SIGNAL TRANSDUCTION;

EID: 78649526394     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri2873     Document Type: Review

References (125)

1. Mossman, B. T. & Churg, A. Mechanisms in the pathogenesis of asbestosis and silicosis. Am. J. Respir. Crit. Care Med. 157, 1666-1680 (1998).
2. Cotran, R. S., Kumar, V. & Robbins, S. in Robbins Pathologic Basis of Disease (ed. Schoen, F. J.) 6-11 (W. B. Saunders Company, Philadelphia, 1994).
3. Cotran, R. S., Kumar, V. & Robbins, S. in Robbins Pathologic Basis of Disease (ed. Schoen, F. J.) 1255-1259 (W. B. Saunders Company, Philadelphia, 1994).
4. Weiner, H. L. & Frenkel, D. Immunology and immunotherapy of Alzheimer's disease. Nature Rev. Immunol. 6, 404-416 (2006).
5. Ross, R. Atherosclerosis - an inflammatory disease. N. Engl. J. Med. 340, 115-126 (1999).
6. Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860-867 (2002).
7. Takeuchi, O. & Akira, S. Pattern recognition receptors and inflammation. Cell 140, 805-820 (2010).
8. Unterholzner, L. et al. IFI16 is an innate immune sensor for intracellular DNA. Nature Immunol. 11, 997-1004 (2010).
9. Matzinger, P. Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12, 991-1045 (1994).
10. Scaffidi, P., Misteli, T. & Bianchi, M. E. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418, 191-195 (2002).
11. Quintana, F. J. & Cohen, I. R. Heat shock proteins as endogenous adjuvants in sterile and septic inflammation. J. Immunol. 175, 2777-2782 (2005).
12. Bours, M. J., Swennen, E. L., Di Virgilio, F., Cronstein, B. N. & Dagnelie, P. C. Adenosine 5?-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol. Ther. 11 2, 358-404 (2006).
13. Kono, H., Chen, C. J., Ontiveros, F. & Rock, K. L. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J. Clin. Invest. 120, 1939-1949 (2010).
14. Babelova, A. et al. Biglycan, a danger signal that activates the NLRP3 inflammasome via Toll-like and P2X receptors. J. Biol. Chem. 284, 24035-24048 (2009).
15. Eigenbrod, T., Park, J. H., Harder, J., Iwakura, Y. & Nunez, G. Cutting edge: critical role for mesothelial cells in necrosis-induced inflammation through the recognition of IL-1α released from dying cells. J. Immunol. 181, 8194-8198 (2008).
16. Moussion, C., Ortega, N. & Girard, J. P. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS ONE 3, e3331 (2008).
17. Kono, H. & Rock, K. L. How dying cells alert the immune system to danger. Nature Rev. Immunol. 8, 279-289 (2008).
18. Basu, S., Binder, R. J., Suto, R., Anderson, K. M. & Srivastava, P. K. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway. Int. Immunol. 12, 1539-1546 (2000).
19. Hofmann, M. A. et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97, 889-901 (1999).
20. Mariathasan, S. et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228-232 (2006).
21. Shi, Y., Evans, J. E. & Rock, K. L. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425, 516-521 (2003).
22. Chen, C. J. et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nature Med. 13, 851-856 (2007).
23. int memory CD8 T cell subset generated under sterile inflammatory conditions. J. Immunol. 182, 3846-3854 (2009).
24. Weber, A. N. et al. Binding of the Drosophila cytokine Spatzle to Toll is direct and establishes signaling. Nature Immunol. 4, 794-800 (2003).
25. Vabulas, R. M. et al. 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. 276, 31332-31339 (2001).
26. Yu, M. et al. HMGB1 signals through Toll-like receptor (TLR) 4 and TLR2. Shock 26, 174-179 (2006).
27. Liu-Bryan, R., Scott, P., Sydlaske, A., Rose, D. M. & Terkeltaub, R. Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 52, 2936-2946 (2005).
28. Gao, B. & Tsan, M. F. Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor α release by murine macrophages. J. Biol. Chem. 278, 174-179 (2003).
29. Rouhiainen, A., Tumova, S., Valmu, L., Kalkkinen, N. & Rauvala, H. Pivotal advance: analysis of proinflammatory activity of highly purified eukaryotic recombinant HMGB1 (amphoterin). J. Leukoc. Biol. 81, 49-58 (2007).
30. Youn, J. H., Oh, Y. J., Kim, E. S., Choi, J. E. & Shin, J. S. High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-α production in human monocytes. J. Immunol. 180, 5067-5074 (2008).
31. Jiang, D. et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nature Med. 11, 1173-1179 (2005).
32. Scheibner, K. A. et al. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J. Immunol. 177, 1272-1281 (2006).
33. Schaefer, L. et al. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J. Clin. Invest. 11 5, 2223-2233 (2005).
34. Kim, S. et al. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457, 102-106 (2009).
35. Mullick, A. E., Tobias, P. S. & Curtiss, L. K. Modulation of atherosclerosis in mice by Toll-like receptor 2. J. Clin. Invest. 11 5, 3149-3156 (2005).
36. Michelsen, K. S. et al. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc. Natl Acad. Sci. USA 101, 10679-10684 (2004).
37. Bjorkbacka, H. et al. Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nature Med. 10, 416-421 (2004).
38. Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 11 6, 3015-3025 (2006).
39. Cavassani, K. A. et al. TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J. Exp. Med. 205, 2609-2621 (2008).
40. Imaeda, A. B. et al. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J. Clin. Invest. 11 9, 305-314 (2009).
41. Kono, H., Karmarkar, D., Iwakura, Y. & Rock, K. L. Identification of the cellular sensor that stimulates the inflammatory response to sterile cell death. J. Immunol. 184, 4470-4478 (2010).
42. Wang, X., Feuerstein, G. Z., Gu, J. L., Lysko, P. G. & Yue, T. L. Interleukin-1β induces expression of adhesion molecules in human vascular smooth muscle cells and enhances adhesion of leukocytes to smooth muscle cells. Atherosclerosis 11 5, 89-98 (1995).
43. Gabay, C., Lamacchia, C. & Palmer, G. IL-1 pathways in inflammation and human diseases. Nature Rev. Rheumatol. 6, 232-241 (2010).
44. Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunol. 9, 847-856 (2008).
45. Raines, E. W., Dower, S. K. & Ross, R. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science 243, 393-396 (1989).
46. Boni-Schnetzler, M. et al. Increased interleukin (IL)-1(3 messenger ribonucleic acid expression in (3-cells of individuals with type 2 diabetes and regulation of IL-1 (3 in human islets by glucose and autostimulation. J. Clin. Endocrinol. Metab. 93 4065-4074 2008.
47. Shoelson, S. E., Lee, J. & Goldfine, A. B. Inflammation and insulin resistance. J. Clin. Invest. 116, 1793-1801 (2006).
48. Burckstummer, T. et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nature Immunol. 10, 266-272 (2009).
49. Fernandes-Alnemri, T., Yu, J. W., Datta, P., Wu, J. & Alnemri, E. S. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509-513 (2009).
50. Hornung, V. et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1 -activating inflammasome with ASC. Nature 458, 514-518 (2009).
51. Fernandes-Alnemri, T. et al. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nature Immunol. 11, 385-393 (2010).
52. Rathinam, V. A. et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nature Immunol. 11, 395-402 (2010).
53. Bauernfeind, F G. et al. Cutting edge: NF-KB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol. 183, 787-791 (2009).
54. Franchi, L, Eigenbrod, T & Nunez, G. Cutting edge: TNF-a mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J. Immunol. 183, 792-796 (2009).
55. Martinon, F, Petrilli, V., Mayor, A., Tardivel, A. & Tschopp, J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237-241 (2006).
56. Halle, A. et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-p. Nature Immunol. 9, 857-865 (2008).
57. Dostert, C. et al. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320, 674-677 (2008).
58. Cassel, S. L. et al. The Nalp3 inflammasome is essential for the development of silicosis. Proc. Natl Acad. Sci. USA 105, 9035-9040 (2008).
59. Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357-1361 (2010).
60. Iyer, S. S. et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl Acad. Sci. USA 106, 20388-20393 (2009).
61. Masters, S. L. et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1 (3 in type 2 diabetes. Nature Immunol. 11, 897-904 (2010).
62. Zhou, R., Tardivel, A., Thorens, B., Choi, I. & Tschopp, J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nature Immunol. 11, 136-140 (2010).
63. el-Moatassim, C. & Dubyak, G. R. A novel pathway for the activation of phospholipase D by P2z purinergic receptors in BAC1.2F5 macrophages. J. Biol. Chem. 267, 23664-23673 (1992).
64. Pelegrin, P. & Surprenant, A. Pannexin-1 mediates large pore formation and interleukin-1 (3 release by the ATP-gated P2X7 receptor. EMBO J. 25, 5071-5082 (2006).
65. Locovei, S., Wang, J. & Dahl, G. Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett. 580, 239-244 (2006).
66. Petrilli, V. et al. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 14, 1583-1589 (2007).
67. Dostert, C. et al. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS ONE 4, e6510 (2009).
68. Fubini, B. & Hubbard, A. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radic. Biol. Med. 34, 1507-1516 (2003).
69. Cruz, C. M. et al. ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J. Biol. Chem. 282, 2871-2879 (2007).
70. Geijtenbeek, T. B. & Gringhuis, S. I. Signalling through C-type lectin receptors: shaping immune responses. Nature Rev. Immunol. 9, 465-479 (2009).
71. Figdor, C. G., van Kooyk, Y. & Adema, G. J. C-type lectin receptors on dendritic cells and Langerhans cells. Nature Rev. Immunol. 2, 77-84 (2002).
72. Yamasaki, S. et al. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nature Immunol. 9, 1179-1188 (2008).
73. Cambi, A. & Figdor, C. Necrosis: C-type lectins sense cell death. Curr. Biol. 19, R375-R378 (2009).
74. Nakamura, N. et al. Isolation and expression profiling of genes upregulated in bone marrow-derived mononuclear cells of rheumatoid arthritis patients. DNA Res. 13, 169-183 (2006).
75. Sancho, D. et al. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458, 899-903 (2009).
76. Rao, D. A. et al. Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection. J. Exp. Med. 205, 3145-3158 (2008).
77. Sakurai, T. et al. Hepatocyte necrosis induced by oxidative stress and IL-1α release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell 14, 156-165 (2008).
78. Cohen, I. et al. Differential release of chromatin-bound IL-1α discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc. Natl Acad. Sci. USA 107, 2574-2579 (2010).
79. Dinarello, C. A. IL-1: discoveries, controversies and future directions. Eur. J. Immunol. 40, 599-606 (2010).
80. Li, P. et al. Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock. Cell 80, 401-411 (1995).
81. Kuida, K. et al. Altered cytokine export and apoptosis in mice deficient in interleukin-1β converting enzyme. Science 267, 2000-2003 (1995).
82. Keller, M., Ruegg, A., Werner, S. & Beer, H. D. Active caspase-1 is a regulator of unconventional protein secretion. Cell 132, 818-831 (2008).
83. Fantuzzi, G. et al. Response to local inflammation of IL-1β-converting enzyme-deficient mice. J. Immunol. 158, 1818-1824 (1997).
84. Mayer-Barber, K. D. et al. Caspase-1 independent IL-1β production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo. J. Immunol. 184, 3326-3330 (2010).
85. Luthi, A. U. et al. Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity 31, 84-98 (2009).
86. Cayrol, C. & Girard, J. P. The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc. Natl Acad. Sci. USA 106, 9021-9026 (2009).
87. Carriere, V. et al. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc. Natl Acad. Sci. USA 104, 282-287 (2007).
88. Verri, W. A. Jr et al. IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy. Ann. Rheum. Dis. 69, 1697-1703 (2010).
89. Fang, F. et al. RAGE-dependent signaling in microglia contributes to neuroinflammation, Aβ accumulation, and impaired learning/memory in a mouse model of Alzheimer's disease. FASEB J. 24, 1043-1055 (2009).
90. Sims, G. P., Rowe, D. C., Rietdijk, S. T., Herbst, R. & Coyle, A. J. HMGB1 and RAGE in inflammation and cancer. Annu. Rev. Immunol. 28, 367-388 (2010).
91. Shang, L. et al. RAGE modulates hypoxia/ reoxygenation injury in adult murine cardiomyocytes via JNK and GSK-3β signaling pathways. PLoS ONE 5, e10092 (2010).
92. Bucciarelli, L. G. et al. RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease. Cell. Mol. Life Sci. 59, 1117-1128 (2002).
93. Hori, O. et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J. Biol. Chem. 270, 25752-25761 (1995).
94. Yan, S. D. et al. RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease. Nature 382, 685-691 (1996).
95. Huang, J. S. et al. Role of receptor for advanced glycation end-product (RAGE) and the JAK/STAT-signaling pathway in AGE-induced collagen production in NRK-49F cells. J. Cell Biochem. 81, 102-113 (2001).
96. Dukic-Stefanovic, S., Schinzel, R., Riederer, P. & Munch, G. AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs? Biogerontology 2, 19-34 (2001).
97. Ishihara, K., Tsutsumi, K., Kawane, S., Nakajima, M. & Kasaoka, T. The receptor for advanced glycation end-products (RAGE) directly binds to ERK by a D-domain-like docking site. FEBS Lett. 550, 107-113 (2003).
98. Tian, J. et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nature Immunol. 8, 487-496 (2007).
99. Ueno, H. et al. Receptor for advanced glycation end-products (RAGE) regulation of adiposity and adiponectin is associated with atherogenesis in apoE-deficient mouse. Atherosclerosis 211, 431-436 (2010).
100. Soro-Paavonen, A. et al. Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in diabetes. Diabetes 57, 2461-2469 (2008).
101. -/- mice. J. Clin. Invest. 11 8, 183-194 (2008).
102. Jiang, D., Liang, J. & Noble, P. W. Hyaluronan in tissue injury and repair. Annu. Rev. Cell Dev. Biol. 23, 435-461 (2007).
103. Taylor, K. R. et al. 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 (2007).
104. Hoebe, K. et al. CD36 is a sensor of diacylglycerides. Nature 433, 523-527 (2005).
105. Stewart, C. R. et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nature Immunol. 11, 155-161 (2010).
106. Chen, G. Y., Tang, J., Zheng, P. & Liu, Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323, 1722-1725 (2009).
107. Liu, Y., Chen, G. Y. & Zheng, P. CD24-Siglec G/10 discriminates danger- from pathogen-associated molecular patterns. Trends Immunol. 30, 557-561 (2009).
108. So, A., De Smedt, T., Revaz, S. & Tschopp, J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res. Ther. 9, R28 (2007).
109. Larsen, C. M. et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 356, 1517-1526 (2007).
110. Larsen, C. M. et al. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care 32, 1663-1668 (2009).
111. Pantschenko, A. G. et al. The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression. Int. J. Oncol. 23, 269-284 (2003).
112. Ghiringhelli, F. et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nature Med. 15, 1170-1178 (2009).
113. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. & Medzhitov, R. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118, 229-241 (2004).
114. Brown, S. L. et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J. Clin. Invest. 11 7, 258-269 (2007).
115. Apetoh, L. et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nature Med. 13, 1050-1059 (2007).
116. Martin, P. & Leibovich, S. J. Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol. 15, 599-607 (2005).
117. DiPietro, L. A. Wound healing: the role of the macrophage and other immune cells. Shock 4, 233-240 (1995).
118. Kroemer, G. et al. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ. 16, 3-11 (2009).
119. Silva, M. T., do Vale, A. & dos Santos, N. M. Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications. Apoptosis 13, 463-482 (2008).
120. Miwa, K. et al. Caspase 1-independent IL-1β release and inflammation induced by the apoptosis inducer Fas ligand. Nature Med. 4, 1287-1292 (1998).
121. Marina-Garcia, N. et al. Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2. J. Immunol. 180, 4050-4057 (2008).
122. Basu, S., Binder, R. J., Ramalingam, T. & Srivastava, P. K. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14, 303-313 (2001).
123. Kariko, K., Ni, H., Capodici, J., Lamphier, M. & Weissman, D. mRNA is an endogenous ligand for Tolllike receptor 3. J. Biol. Chem. 279, 12542-12550 (2004).
124. Johnson, G. B., Brunn, G. J., Kodaira, Y. & Platt, J. L. Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J. Immunol. 168, 5233-5239 (2002).
125. Zhang, Q. et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464, 104-107 (2010).