Toll-like receptor 4 signaling in intracerebral hemorrhage-induced inflammation and injury

Journal of Neuroinflammation

Volumn 10, Issue , 2013, Pages

  Fang, Huang ^a   Wang, Peng Fei ^a   Zhou, Yu ^a   Wang, Yan Chun ^a   Yang, Qing Wu ^a  

^a THIRD MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Hematoma resolution; Inflammation; Intracerebral hemorrhage; Toll like receptor 4

Indexed keywords

HAPTOGLOBIN; HEME; NEUROPROTECTIVE AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROGESTERONE; REACTIVE OXYGEN METABOLITE; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 4 ANTAGONIST; TOLL LIKE RECEPTOR 4 ANTIBODY; UNCLASSIFIED DRUG; TLR4 PROTEIN, HUMAN;

BRAIN HEMATOMA; BRAIN HEMORRHAGE; BRAIN INJURY; BRAIN REGION; CELL ACTIVATION; CYTOKINE PRODUCTION; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG TARGETING; ENCEPHALITIS; GENE DELETION; GENE EXPRESSION REGULATION; HUMAN; INNATE IMMUNITY; MICROGLIA; MOLECULAR DYNAMICS; MOLECULAR PATHOLOGY; NEUROPROTECTION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; RECEPTOR DOWN REGULATION; RECEPTOR UPREGULATION; REVIEW; SIGNAL TRANSDUCTION; SUBARACHNOID HEMORRHAGE; TOLL LIKE RECEPTOR 4 GENE; ANIMAL; IMMUNOLOGY; METABOLISM; PATHOLOGY; PHYSIOLOGY;

ANIMALS; BRAIN INJURIES; CEREBRAL HEMORRHAGE; HUMANS; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 4;

EID: 84873743908     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/1742-2094-10-27     Document Type: Review

References (118)

1. Hwang BY, Appelboom G, Ayer A, Kellner CP, Kotchetkov IS, Gigante PR, Haque R, Kellner M, Connolly ES. Advances in neuroprotective strategies: potential therapies for intracerebral hemorrhage. Cerebrovasc Dis 2011, 31(3):211-222. 10.1159/000321870, 21178344.
2. Flower O, Smith M. The acute management of intracerebral hemorrhage. Curr Opin Crit Care 2011, 17(2):106-114. 10.1097/MCC.0b013e328342f823, 21169826.
3. Mayer SA, Rincon F. Treatment of intracerebral haemorrhage. Lancet Neurol 2005, 4(10):662-672. 10.1016/S1474-4422(05)70195-2, 16168935.
4. Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006, 5(1):53-63. 10.1016/S1474-4422(05)70283-0, 16361023.
5. Babu R, Bagley JH, Di C, Friedman AH, Adamson C. Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention. Neurosurg Focus 2012, 32(4):E8. 10.3171/2012.1.FOCUS11366, 22655697.
6. Elliott J, Smith M. The acute management of intracerebral hemorrhage: a clinical review. Anesth Analg 2010, 110(5):1419-1427. 10.1213/ANE.0b013e3181d568c8, 20332192.
7. Felberg RA, Grotta JC, Shirzadi AL, Strong R, Narayana P, Hill-Felberg SJ, Aronowski J. Cell death in experimental intracerebral hemorrhage: the " black hole" model of hemorrhagic damage. Ann Neurol 2002, 51(4):517-524. 10.1002/ana.10160, 11921058.
8. Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT. Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg 2002, 96(2):287-293. 10.3171/jns.2002.96.2.0287, 11838803.
9. Lee KR, Kawai N, Kim S, Sagher O, Hoff JT. Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model. J Neurosurg 1997, 86(2):272-278. 10.3171/jns.1997.86.2.0272, 9010429.
10. Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke 2011, 42(6):1781-1786. 10.1161/STROKEAHA.110.596718, 3123894, 21527759.
11. Sharp F, Liu DZ, Zhan X, Ander BP. Intracerebral hemorrhage injury mechanisms: glutamate neurotoxicity, thrombin, and Src. Acta Neurochir Suppl 2008, 105:43-46. 10.1007/978-3-211-09469-3_9, 19066080.
12. Wagner KR, Packard BA, Hall CL, Smulian AG, Linke MJ, De Courten-Myers GM, Packard LM, Hall NC. Protein oxidation and heme oxygenase-1 induction in porcine white matter following intracerebral infusions of whole blood or plasma. Dev Neurosci 2002, 24(2-3):154-160.
13. Nakamura T, Keep RF, Hua Y, Hoff JT, Xi G. Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res 2005, 1039(1-2):30-36.
14. Robinson SR, Dang TN, Dringen R, Bishop GM. Hemin toxicity: a preventable source of brain damage following hemorrhagic stroke. Redox Rep 2009, 14(6):228-235. 10.1179/135100009X12525712409931, 20003707.
15. Yenari MA, Xu L, Tang XN, Qiao Y, Giffard RG. Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke 2006, 37(4):1087-1093. 10.1161/01.STR.0000206281.77178.ac, 16497985.
16. Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab 2007, 27(5):894-908.
17. Gautier S, Ouk T, Petrault O, Caron J, Bordet R. Neutrophils contribute to intracerebral haemorrhages after treatment with recombinant tissue plasminogen activator following cerebral ischaemia. Br J Pharmacol 2009, 156(4):673-679. 10.1111/j.1476-5381.2009.00068.x, 2697703, 19210512.
18. Moxon-Emre I, Schlichter LC. Neutrophil depletion reduces blood-brain barrier breakdown, axon injury, and inflammation after intracerebral hemorrhage. J Neuropathol Exp Neurol 2011, 70(3):218-235. 10.1097/NEN.0b013e31820d94a5, 21293296.
19. Nguyen HX, O'Barr TJ, Anderson AJ. Polymorphonuclear leukocytes promote neurotoxicity through release of matrix metalloproteinases, reactive oxygen species, and TNF-α. J Neurochem 2007, 102(3):900-912. 10.1111/j.1471-4159.2007.04643.x, 17561941.
20. Wang J. Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol 2010, 92(4):463-477. 10.1016/j.pneurobio.2010.08.001, 2991407, 20713126.
21. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006, 124(4):783-801. 10.1016/j.cell.2006.02.015, 16497588.
22. Kong Y, Le Y. Toll-like receptors in inflammation of the central nervous system. Int Immunopharmacol 2011, 11(10):1407-1414. 10.1016/j.intimp.2011.04.025, 21600311.
23. Beutler BA. TLRs and innate immunity. Blood 2009, 113(7):1399-1407. 2644070, 18757776.
24. Zhu J, Mohan C. Toll-like receptor signaling pathways: therapeutic opportunities. Mediators Inflamm 2010, 2010:781235. 2963142, 20981241.
25. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004, 4(7):499-511. 10.1038/nri1391, 15229469.
26. Takeda K, Akira S. TLR signaling pathways. Semin Immunol 2004, 16(1):3-9. 10.1016/j.smim.2003.10.003, 14751757.
27. Lin Q, Li M, Fang D, Fang J, Su SB. The essential roles of Toll-like receptor signaling pathways in sterile inflammatory diseases. Int Immunopharmacol 2011, 11(10):1422-1432. 10.1016/j.intimp.2011.04.026, 21600309.
28. Lin S, Yin Q, Zhong Q, Lv FL, Zhou Y, Li JQ, Wang JZ, Su BY, Yang QW. Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage. J Neuroinflammation 2012, 9:46. 10.1186/1742-2094-9-46, 3344687, 22394415.
29. Teng W, Wang L, Xue W, Guan C. Activation of TLR4-mediated NF-κB signaling in hemorrhagic brain in rats. Mediators Inflamm 2009, 2009:473276. 2817507, 20150961.
30. Ma CX, Yin WN, Cai BW, Wu J, Wang JY, He M, Sun H, Ding JL, You C. Toll-like receptor 4/nuclear factor-κ B signaling detected in brain after early subarachnoid hemorrhage. Chin Med J (Engl) 2009, 122(13):1575-1581.
31. Sansing LH, Harris TH, Welsh FA, Kasner SE, Hunter CA, Kariko K. Toll-like receptor 4 contributes to poor outcome after intracerebral hemorrhage. Ann Neurol 2011, 70(4):646-656. 10.1002/ana.22528, 22028224.
32. Figueiredo RT, Fernandez PL, Mourao-Sa DS, Porto BN, Dutra FF, Alves LS, Oliveira MF, Oliveira PL, Graça-Souza AV, Bozza MT. Characterization of heme as activator of Toll-like receptor 4. J Biol Chem 2007, 282(28):20221-20229. 10.1074/jbc.M610737200, 17502383.
33. Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through Toll-like receptor 4. J Immunol 2001, 167(5):2887-2894.
34. Aronowski J, Hall CE. New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies. Neurol Res 2005, 27(3):268-279. 10.1179/016164105X25225, 15845210.
35. Xue M, Del Bigio MR. Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death. Neurosci Lett 2000, 283(3):230-232. 10.1016/S0304-3940(00)00971-X, 10754230.
36. Zhao X, Grotta J, Gonzales N, Aronowski J. Hematoma resolution as a therapeutic target: the role of microglia/macrophages. Stroke 2009, 40(3 Suppl):S92-S94.
37. Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, Grotta JC, Aronowski J. Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor γ in microglia/macrophages. Ann Neurol 2007, 61(4):352-362. 10.1002/ana.21097, 17457822.
38. Wang J, Tsirka SE. Contribution of extracellular proteolysis and microglia to intracerebral hemorrhage. Neurocrit Care 2005, 3(1):77-85. 10.1385/NCC:3:1:077, 16159103.
39. Gao Z, Wang J, Thiex R, Rogove AD, Heppner FL, Tsirka SE. Microglial activation and intracerebral hemorrhage. Acta Neurochir Suppl 2008, 105:51-53. 10.1007/978-3-211-09469-3_11, 19066082.
40. Wang J, Rogove AD, Tsirka AE, Tsirka SE. Protective role of tuftsin fragment 1-3 in an animal model of intracerebral hemorrhage. Ann Neurol 2003, 54(5):655-664. 10.1002/ana.10750, 14595655.
41. Wang J, Tsirka SE. Tuftsin fragment 1-3 is beneficial when delivered after the induction of intracerebral hemorrhage. Stroke 2005, 36(3):613-618. 10.1161/01.STR.0000155729.12931.8f, 15692122.
42. Wu J, Yang S, Xi G, Fu G, Keep RF, Hua Y. Minocycline reduces intracerebral hemorrhage-induced brain injury. Neurol Res 2009, 31(2):183-188. 10.1179/174313209X385680, 2659336, 19061541.
43. Wu J, Yang S, Hua Y, Liu W, Keep RF, Xi G. Minocycline attenuates brain edema, brain atrophy and neurological deficits after intracerebral hemorrhage. Acta Neurochir Suppl 2010, 106:147-150. 10.1007/978-3-211-98811-4_26, 19812938.
44. Zhao F, Hua Y, He Y, Keep RF, Xi G. Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke 2011, 42(12):3587-3593. 10.1161/STROKEAHA.111.623926, 3226873, 21998050.
45. Wasserman JK, Schlichter LC. Minocycline protects the blood-brain barrier and reduces edema following intracerebral hemorrhage in the rat. Exp Neurol 2007, 207(2):227-237. 10.1016/j.expneurol.2007.06.025, 17698063.
46. Wang J, Dore S. Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage. Brain 2007, 130(Pt 6):1643-1652. 2291147, 17525142.
47. Turrin NP, Plata-Salaman CR. Cytokine-cytokine interactions and the brain. Brain Res Bull 2000, 51(1):3-9. 10.1016/S0361-9230(99)00203-8, 10654575.
48. Emsley HC, Tyrrell PJ. Inflammation and infection in clinical stroke. J Cereb Blood Flow Metab 2002, 22(12):1399-1419.
49. Hua Y, Wu J, Keep RF, Nakamura T, Hoff JT, Xi G. Tumor necrosis factor-α increases in the brain after intracerebral hemorrhage and thrombin stimulation. Neurosurgery 2006, 58(3):542-550. discussion 542-550.
50. Zhang X, Li H, Hu S, Zhang L, Liu C, Zhu C, Liu R, Li C. Brain edema after intracerebral hemorrhage in rats: the role of inflammation. Neurol India 2006, 54(4):402-407. 10.4103/0028-3886.28115, 17114852.
51. Castillo J, Dávalos A, Alvarez-Sabín J, Pumar JM, Leira R, Silva Y, Montaner J, Kase CS. Molecular signatures of brain injury after intracerebral hemorrhage. Neurology 2002, 58(4):624-629. 10.1212/WNL.58.4.624, 11865143.
52. Chen YC, Hu FJ, Chen P, Wu YR, Wu HC, Chen ST, Lee-Chen GJ, Chen CM. Association of TNF-α gene with spontaneous deep intracerebral hemorrhage in the Taiwan population: a case control study. BMC Neurol 2010, 10:41. 10.1186/1471-2377-10-41, 2891694, 20534169.
53. Wu J, Yang S, Xi G, Song S, Fu G, Keep RF, Hua Y. Microglial activation and brain injury after intracerebral hemorrhage. Acta Neurochir Suppl 2008, 105:59-65. 10.1007/978-3-211-09469-3_13, 19066084.
54. Holmin S, Mathiesen T. Intracerebral administration of interleukin-1β and induction of inflammation, apoptosis, and vasogenic edema. J Neurosurg 2000, 92(1):108-120. 10.3171/jns.2000.92.1.0108, 10616089.
55. Wagner KR. Modeling intracerebral hemorrhage: glutamate, nuclear factor-κB signaling and cytokines. Stroke 2007, 38(2 Suppl):753-758.
56. Zhao X, Zhang Y, Strong R, Zhang J, Grotta JC, Aronowski J. Distinct patterns of intracerebral hemorrhage-induced alterations in NF-κB subunit, iNOS, and COX-2 expression. J Neurochem 2007, 101(3):652-663.
57. Allan SM, Rothwell NJ. Inflammation in central nervous system injury. Philos Trans R Soc Lond B Biol Sci 2003, 358(1438):1669-1677. 10.1098/rstb.2003.1358, 1693261, 14561325.
58. Hickenbottom SL, Grotta JC, Strong R, Denner LA, Aronowski J. Nuclear factor-κB and cell death after experimental intracerebral hemorrhage in rats. Stroke 1999, 30(11):2472-2477. discussion 2477-2478, 10.1161/01.STR.30.11.2472, 10548686.
59. Wang YX, Yan A, Ma ZH, Wang Z, Zhang B, Ping JL, Zhu JS, Zhou Y, Dai L. Nuclear factor-κB and apoptosis in patients with intracerebral hemorrhage. J Clin Neurosci 2011, 18(10):1392-1395. 10.1016/j.jocn.2010.11.039, 21782444.
60. Barton GM, Medzhitov R. Control of adaptive immune responses by Toll-like receptors. Curr Opin Immunol 2002, 14(3):380-383. 10.1016/S0952-7915(02)00343-6, 11973138.
61. Brown J, Wang H, Hajishengallis GN, Martin M. TLR-signaling networks: an integration of adaptor molecules, kinases, and cross-talk. J Dent Res 2011, 90(4):417-427. 10.1177/0022034510381264, 3075579,3075579, 20940366.
62. Shi XQ, Zekki H, Zhang J. The role of TLR2 in nerve injury-induced neuropathic pain is essentially mediated through macrophages in peripheral inflammatory response. Glia 2011, 59(2):231-241. 10.1002/glia.21093, 21125644.
63. Wu FX, Bian JJ, Miao XR, Huang SD, Xu XW, Gong DJ, Sun YM, Lu ZJ, Yu WF. Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain. Int J Med Sci 2010, 7(5):251-259. 2920570, 20714435.
64. Hanamsagar R, Hanke ML, Kielian T. Toll-like receptor (TLR) and inflammasome actions in the central nervous system. Trends Immunol 2012, 33(7):333-342. 10.1016/j.it.2012.03.001, 22521509.
65. Shichita T, Sakaguchi R, Suzuki M, Yoshimura A. Post-ischemic inflammation in the brain. Front Immunol 2012, 3:132. 3400935, 22833743.
66. Hyakkoku K, Hamanaka J, Tsuruma K, Shimazawa M, Tanaka H, Uematsu S, Akira S, Inagaki N, Nagai H, Hara H. Toll-like receptor 4 (TLR4), but not TLR3 or TLR9, knock-out mice have neuroprotective effects against focal cerebral ischemia. Neuroscience 2010, 171(1):258-267. 10.1016/j.neuroscience.2010.08.054, 20804821.
67. Caso JR, Pradillo JM, Hurtado O, Lorenzo P, Moro MA, Lizasoain I. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 2007, 115(12):1599-1608. 10.1161/CIRCULATIONAHA.106.603431, 17372179.
68. Rodríguez-Yáñez M, Brea D, Arias S, Blanco M, Pumar JM, Castillo J, Sobrino T. Increased expression of Toll-like receptors 2 and 4 is associated with poor outcome in intracerebral hemorrhage. J Neuroimmunol 2012, 247(1-2):75-80.
69. Yang QW, Lu FL, Zhou Y, Wang L, Zhong Q, Lin S, Xiang J, Li JC, Fang CQ, Wang JZ. HMBG1 mediates ischemia-reperfusion injury by TRIF-adaptor independent Toll-like receptor 4 signaling. J Cereb Blood Flow Metab 2011, 31(2):593-605. 10.1038/jcbfm.2010.129, 3049514, 20700129.
70. Carty M, Bowie AG. Evaluating the role of Toll-like receptors in diseases of the central nervous system. Biochem Pharmacol 2011, 81(7):825-837. 10.1016/j.bcp.2011.01.003, 21241665.
71. Aravalli RN, Peterson PK, Lokensgard JR. Toll-like receptors in defense and damage of the central nervous system. J Neuroimmune Pharmacol 2007, 2(4):297-312. 10.1007/s11481-007-9071-5, 18040848.
72. Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MAD, Nacken W, Foell D, van der Poll T, Sorg C, Roth J. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 2007, 13(9):1042-1049. 10.1038/nm1638, 17767165.
73. Buchanan MM, Hutchinson M, Watkins LR, Yin H. Toll-like receptor 4 in CNS pathologies. J Neurochem 2010, 114(1):13-27. 2909662, 20402965.
74. O'Neill LA. How Toll-like receptors signal: what we know and what we don't know. Curr Opin Immunol 2006, 18(1):3-9. 10.1016/j.coi.2005.11.012, 16343886.
75. Jochum W, Passegue E, Wagner EF. AP-1 in mouse development and tumorigenesis. Oncogene 2001, 20(19):2401-2412. 10.1038/sj.onc.1204389, 11402336.
76. Kawai T, Akira S. TLR signaling. Cell Death Differ 2006, 13(5):816-825. 10.1038/sj.cdd.4401850, 16410796.
77. Vincenti MP, Brinckerhoff CE. Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res Ther 2002, 4(3):157-164.
78. Wasserman JK, Zhu X, Schlichter LC. Evolution of the inflammatory response in the brain following intracerebral hemorrhage and effects of delayed minocycline treatment. Brain Res 2007, 1180:140-154.
79. Xue M, Fan Y, Liu S, Zygun DA, Demchuk A, Yong VW. Contributions of multiple proteases to neurotoxicity in a mouse model of intracerebral haemorrhage. Brain 2009, 132:26-36.
80. Michel-Monigadon D, Bonny C, Hirt L. c-Jun N-terminal kinase pathway inhibition in intracerebral hemorrhage. Cerebrovasc Dis 2010, 29(6):564-570. 10.1159/000306643, 20375499.
81. Lively S, Schlichter LC. Age-related comparisons of evolution of the inflammatory response after intracerebral hemorrhage in rats. Transl Stroke Res 2012, 3(Suppl 1):132-146. 3372776, 22707991.
82. Boehmer ED, Goral J, Faunce DE, Kovacs EJ. Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression. J Leukoc Biol 2004, 75(2):342-349.
83. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, El Khoury J, Golenbock DT, Moore KJ. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 2010, 11(2):155-161. 10.1038/ni.1836, 2809046, 20037584.
84. Ohashi K, Burkart V, Flohe S, Kolb H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 2000, 164(2):558-561.
85. Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 2002, 277(17):15107-15112. 10.1074/jbc.M111204200, 11842086.
86. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC. Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med 2002, 195(1):99-111. 10.1084/jem.20001858, 2196009, 11781369.
87. Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem 2004, 279(17):17079-17084. 10.1074/jbc.M310859200, 14764599.
88. Mata-Haro V, Cekic C, Martin M, Chilton PM, Casella CR, Mitchell TC. The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science 2007, 316(5831):1628-1632. 10.1126/science.1138963, 17569868.
89. Gangloff M. Different dimerisation mode for TLR4 upon endosomal acidification?. Trends Biochem Sci 2012, 37(3):92-98. 10.1016/j.tibs.2011.11.003, 3323831, 22196451.
90. Schmidt P, Krook H, Goto M, Korsgren O. MyD88-dependent toll-like receptor signalling is not a requirement for fetal islet xenograft rejection in mice. Xenotransplantation 2004, 11(4):347-352. 10.1111/j.1399-3089.2004.00145.x, 15196129.
91. Murakami K, Koide M, Dumont TM, Russell SR, Tranmer BI, Wellman GC. Subarachnoid hemorrhage induces gliosis and increased expression of the pro-inflammatory cytokine high mobility group box 1 protein. Transl Stroke Res 2011, 2(1):72-79. 10.1007/s12975-010-0052-2, 3072171, 21479116.
92. Ohnishi M, Katsuki H, Fukutomi C, Takahashi M, Motomura M, Fukunaga M, Matsuoka Y, Isohama Y, Izumi Y, Kume T, Inoue A, Akaike A. HMGB1 inhibitor glycyrrhizin attenuates intracerebral hemorrhage-induced injury in rats. Neuropharmacology 2011, 61(5-6):975-980.
93. Kanzler H, Barrat FJ, Hessel EM, Coffman RL. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat Med 2007, 13(5):552-559. 10.1038/nm1589, 17479101.
94. Liu X, Zheng J, Zhou H. TLRs as pharmacological targets for plant-derived compounds in infectious and inflammatory diseases. Int Immunopharmacol 2011, 11(10):1451-1456. 10.1016/j.intimp.2011.04.027, 21586344.
95. Gearing AJ. Targeting toll-like receptors for drug development: a summary of commercial approaches. Immunol Cell Biol 2007, 85(6):490-494. 10.1038/sj.icb.7100102, 17667933.
96. Park SJ, Kang SH, Kang YK, Eom YB, Koh KO, Kim DY, Youn HS. Inhibition of homodimerization of toll-like receptor 4 by 4-oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester. Int Immunopharmacol 2011, 11(1):19-22. 10.1016/j.intimp.2010.09.020, 20939996.
97. Youn HS, Saitoh SI, Miyake K, Hwang DH. Inhibition of homodimerization of Toll-like receptor 4 by curcumin. Biochem Pharmacol 2006, 72(1):62-69. 10.1016/j.bcp.2006.03.022, 16678799.
98. Ahn SI, Lee JK, Youn HS. Inhibition of homodimerization of toll-like receptor 4 by 6-shogaol. Mol Cells 2009, 27(2):211-215. 10.1007/s10059-009-0026-y, 19277504.
99. Park SJ, Youn HS. Suppression of homodimerization of Toll-like receptor 4 by isoliquiritigenin. Phytochemistry 2010, 71(14-15):1736-1740.
100. Liang Q, Wu Q, Jiang J, Duan J, Wang C, Smith MD, Lu H, Wang Q, Nagarkatti P, Fan D. Characterization of sparstolonin B, a Chinese herb-derived compound, as a selective Toll-like receptor antagonist with potent anti-inflammatory properties. J Biol Chem 2011, 286(30):26470-26479. 10.1074/jbc.M111.227934, 3143611, 21665946.
101. Park SJ, Lee AN, Youn HS. TBK1-targeted suppression of TRIF-dependent signaling pathway of toll-like receptor 3 by auranofin. Arch Pharm Res 2010, 33(6):939-945. 10.1007/s12272-010-0618-2, 20607500.
102. Kuno M, Nemoto K, Ninomiya N, Inagaki E, Kubota M, Matsumoto T, Yokota H. The novel selective toll-like receptor 4 signal transduction inhibitor tak-242 prevents endotoxaemia in conscious guinea-pigs. Clin Exp Pharmacol Physiol 2009, 36(5-6):589-593.
103. Nakamura M, Shimizu Y, Sato Y, Miyazaki Y, Satoh T, Mizuno M, Kato Y, Hosaka Y, Furusako S. Toll-like receptor 4 signal transduction inhibitor, M62812, suppresses endothelial cell and leukocyte activation and prevents lethal septic shock in mice. Eur J Pharmacol 2007, 569(3):237-243. 10.1016/j.ejphar.2007.05.013, 17588563.
104. Huang M, Hu YY, Dong XQ, Xu QP, Yu WH, Zhang ZY. The protective role of oxymatrine on neuronal cell apoptosis in the hemorrhagic rat brain. J Ethnopharmacol 2012, 143(1):228-235. 10.1016/j.jep.2012.06.028, 22750437.
105. Yu WH, Dong XQ, Hu YY, Huang M, Zhang ZY. Ginkgolide B reduces neuronal cell apoptosis in the traumatic rat brain: possible involvement of Toll-like receptor 4 and nuclear factor κB pathway. Phytother Res 2012, 26(12):1838-1844. 10.1002/ptr.4662, 22422608.
106. Wang Z, Zuo G, Shi XY, Zhang J, Fang Q, Chen G. Progesterone administration modulates cortical TLR4/NF-κB signaling pathway after subarachnoid hemorrhage in male rats. Mediators Inflamm 2011, 2011:848309. 3051156, 21403869.
107. Tasaki K, Ruetzler CA, Ohtsuki T, Martin D, Nawashiro H, Hallenbeck JM. Lipopolysaccharide pre-treatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats. Brain Res 1997, 748(1-2):267-270.
108. Rosenzweig HL, Lessov NS, Henshall DC, Minami M, Simon RP, Stenzel-Poore MP. Endotoxin preconditioning prevents cellular inflammatory response during ischemic neuroprotection in mice. Stroke 2004, 35(11):2576-2581. 10.1161/01.STR.0000143450.04438.ae, 15375302.
109. Vartanian KB, Stevens SL, Marsh BJ, Williams-Karnesky R, Lessov NS, Stenzel-Poore MP. LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury. J Neuroinflammation 2011, 8:140. 10.1186/1742-2094-8-140, 3217906, 21999375.
110. Stevens SL, Leung PY, Vartanian KB, Gopalan B, Yang T, Simon RP, Stenzel-Poore MP. Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury. J Neurosci 2011, 31(23):8456-8463. 10.1523/JNEUROSCI.0821-11.2011, 3130521, 21653850.
111. Wagner KR, Sharp FR, Ardizzone TD, Lu A, Clark JF. Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab 2003, 23(6):629-652.
112. Zhao X, Song S, Sun G, Strong R, Zhang J, Grotta JC, Aronowski J. Neuroprotective role of haptoglobin after intracerebral hemorrhage. J Neurosci 2009, 29(50):15819-15827. 10.1523/JNEUROSCI.3776-09.2009, 2831226, 20016097.
113. Zhao X, Sun G, Zhang J, Strong R, Dash PK, Kan YW, Grotta JC, Aronowski J. Transcription factor Nrf2 protects the brain from damage produced by intracerebral hemorrhage. Stroke 2007, 38(12):3280-3286. 10.1161/STROKEAHA.107.486506, 17962605.
114. Chen G, Fang Q, Zhang J, Zhou D, Wang Z. Role of the Nrf2-ARE pathway in early brain injury after experimental subarachnoid hemorrhage. J Neurosci Res 2011, 89(4):515-523. 10.1002/jnr.22577, 21259333.
115. Fadok VA, Warner ML, Bratton DL, Henson PM. CD36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor (αvvβ3). J Immunol 1998, 161(11):6250-6257.
116. Ren Y, Silverstein RL, Allen J, Savill J. CD36 gene transfer confers capacity for phagocytosis of cells undergoing apoptosis. J Exp Med 1995, 181(5):1857-1862. 10.1084/jem.181.5.1857, 2192004, 7536797.
117. Zhao X, Zhang Y, Strong R, Grotta JC, Aronowski J. 15d-prostaglandin J2 activates peroxisome proliferator-activated receptor-γ, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats. J Cereb Blood Flow Metab 2006, 26(6):811-820. 10.1038/sj.jcbfm.9600233, 16208315.
118. Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature 2004, 430(6996):257-263. 10.1038/nature02761, 15241424.