Toll-like receptors in spinal cord injury

Current Topics in Microbiology and Immunology

Volumn 336, Issue 1, 2009, Pages 121-136

  Kigerl, Kristina A ^a   Popovich, Phillip G ^a  

^a THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 6; TOLL LIKE RECEPTOR 8;

ANTIGEN RECOGNITION; CELL ACTIVATION; CELL METABOLISM; DANGER ASSOCIATED MOLECULAR PATTERN; DEMYELINATION; GLIA CELL; GROWTH CONE; HOST RESISTANCE; LEUKOCYTE; MOLECULE; NERVE DEGENERATION; NERVE REGENERATION; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SPINAL CORD INJURY; STEM CELL; TISSUE INJURY; ANIMAL; HUMAN; IMMUNOLOGY;

ANIMALS; HUMANS; NERVE DEGENERATION; NERVE REGENERATION; SPINAL CORD INJURIES; TOLL-LIKE RECEPTORS;

EID: 77951650473     PISSN: 0070217X     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-3-642-00549-7_7     Document Type: Review

References (106)

1. Anderson K V, Bokla L, Nusslein-Volhard C (1985) Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell 42:791-798
2. Ankeny DP, McTigue DM, Guan Z, Yan Q, Kinstler O, Stokes BT, Jakeman LB (2001) Pegylated brain-derived neurotrophic factor shows improved distribution into the spinal cord and stimulates locomotor activity and morphological changes after injury. Exp Neurol 170:85-100
3. Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277:15028-15034
4. Babb A, Carlson WO (2006) Spinal stenosis. S D Med 59:103-105
5. Balentine JD (1978a) Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest 39:236-253
6. Balentine JD (1978b) Pathology of experimental spinal cord trauma. II Ultrastructure of axons and myelin. Lab Invest 39:254-266
7. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW (1993) Cytotoxicity of microglia. Glia 7:111-118
8. Bao F, Chen Y, Dekaban GA, Weaver LC (2004) Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats. J Neurochem 88:1335-1344
9. Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol 12:1539-1546
10. Bethea JR, Castro M, Keane RW, Lee TT, Dietrich WD, Yezierski RP (1998) Traumatic spinal cord injury induces nuclear factor-kB activation. J Neurosci 18:3251-3260
11. Bethea JR, Nagashima H, Acosta MC, Briceno C, Gomez F, Marcillo AE, Loor K, Green J, Dietrich WD (1999) Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma 16:851-863
12. Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1-5
13. Blight AR (1994) Effects of silica on the outcome from experimental spinal cord injury: implication of macrophages in secondary tissue damage. Neuroscience 60:263-273
14. Bowman CC, Rasley A, Tranguch SL, Marriott I (2003) Cultured astrocytes express toll-like receptors for bacterial products. Glia 43:281-291
15. Bradbury EJ, McMahon SB (2006) Spinal cord repair strategies: why do they work? Nat Rev Neurosci 7:644-653
16. Bronstein DM, Perez-Otano I, Sun V, Mullis Sawin SB, Chan J, Wu GC, Hudson PM, Kong LY, Hong JS, McMillian MK (1995) Glia-dependent neurotoxicity and neuroprotection in mesen-cephalic cultures. Brain Res 704:112-116
17. Bsibsi M, Persoon-Deen C, Verwer RW, Meeuwsen S, Ravid R, van Noort JM (2006) Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators. Glia 53:688-695
18. Bsibsi M, Ravid R, Gveric D, van Noort JM (2002) Broad expression of Toll-like receptors in the human central nervous system. J Neuropathol Exp Neurol 61:1013-1021
19. Cameron JS, Alexopoulou L, Sloane JA, DiBernardo AB, Ma Y, Kosaras B, Flavell R, Strittmatter SM, Volpe J, Sidman R, Vartanian T (2007) Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals. J Neurosci 27:13033-13041
20. Chang HT (2007) Subacute human spinal cord contusion: few lymphocytes and many mac-rophages. Spinal Cord 45:174-182
21. Clemente CD, Windle WF (1954) Regeneration of severed nerve fibers in the spinal cord of the adult cat. J Comp Neurol 101:691-731
22. Davis AE, Campbell SJ, Wilainam P, Anthony DC (2005) Post-conditioning with lipopolysac-charide reduces the inflammatory infiltrate to the injured brain and spinal cord: a potential neuroprotective treatment. Eur J Neurosci 22:2441-2450
23. Deng JC, Cheng G, Newstead MW, Zeng X, Kobayashi K, Flavell RA, Standiford TJ (2006) Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. J.Clin.Invest 116:2532-2542
24. Dusart I, Schwab ME (1994) Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J Neurosci 6:712-724
25. Elkabes S, DiCicco-Bloom EM, Black IB (1996) Brain microglia/macrophages express neurotro-phins that selectively regulate microglial proliferation and function. J Neurosci 16:2508-2521
26. Esen N, Tanga F Y, DeLeo JA, Kielian T (2004) Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus. J Neurochem 88:746-758
27. Farhat K, Riekenberg S, Heine H, Debarry J, Lang R, Mages J, Buwitt-Beckmann U, Roschmann K, Jung G, Wiesmuller KH, Ulmer AJ (2008) Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling. J Leukoc Biol 83:692-701
28. Felts PA, Woolston AM, Fernando HB, Asquith S, Gregson NA, Mizzi OJ, Smith KJ (2005) Inflammation and primary demyelination induced by the intraspinal injection of lipopolysac-charide. Brain 128:1649-1666
29. Fitch MT, Doller C, Combs CK, Landreth GE, Silver J (1999) Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci 19:8182-8198
30. Fleming JC, Norenberg MD, Ramsay DA, Dekaban GA, Marcillo AE, Saenz AD, Pasquale-Styles M, Dietrich WD, Weaver LC (2006) The cellular inflammatory response in human spinal cords after injury. Brain 129:3249-3269
31. Gensel SC, Nakamura S, Van Rooijen N, Ankeny DP, Popovich PG (2009) Macrophages promote axon regeneration with concurrent neurotoxicity. J Neurosci 29(12):3956-68
32. Giulian D, Robertson C (1990) Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann Neurol 27:33-42
33. Gris D, Marsh DR, Oatway MA, Chen Y, Hamilton EF, Dekaban GA, Weaver LC (2004) Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci 24:4043-4051
34. Guth L, Zhang Z, DiProspero NA, Joubin K, Fitch MT (1994a) Spinal cord injury in the rat: treatment with bacterial lipopolysaccharide and indomethacin enhances cellular repair and locomotor function. Exp Neurol 126:76-87
35. Guth L, Zhang Z, Roberts E (1994b) Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. Proc Natl Acad Sci USA 91:12308-12312
36. Johnson GB, Brunn GJ, Kodaira Y, Platt JL (2002) Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J Immunol 168: 5233-5239
37. Jung DY, Lee H, Jung BY, Ock J, Lee MS, Lee WH, Suk K (2005) TLR4, but not TLR2, signals autoregulatory apoptosis of cultured microglia: a critical role of IFN-beta as a decision maker. J Immunol 174:6467-6476
38. Kariko K, Ni H, Capodici J, Lamphier M, Weissman D (2004) mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem 279:12542-12550
39. Kielian T, Esen N, Bearden ED (2005a) Toll-like receptor 2 (TLR2) is pivotal for recognition of S. aureus peptidoglycan but not intact bacteria by microglia. Glia 49:567-576
40. Kielian T, Haney A, Mayes PM, Garg S, Esen N (2005b) Toll-like receptor 2 modulates the proin-flammatory milieu in Staphylococcus aureus-induced brain abscess. Infect Immun 73:7428-7435
41. Kigerl KA, Lai W, Rivest S, Hart RP, Satoskar AR, Popovich PG (2007) Toll-like receptor (TLR)-2 and TLR-4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury. J Neurochem 102:37-50
42. Kigerl KA, McGaughy VM, Popovich PG (2006) Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury. Comp Neurol 494:578-594
43. Kim GM, Xu J, Xu J, Song SK, Yan P, Ku G, Xu XM, Hsu CY (2001) Tumor necrosis factor receptor deletion reduces nuclear factor-kappaB activation, cellular inhibitor of apoptosis protein 2 expression, and functional recovery after traumatic spinal cord injury. J Neurosci 21:6617-6625
44. Kim WG, Mohney RP, Wilson B, Jeohn GH, Liu B, Hong JS (2000) Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci 20:6309-6316
45. Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M, Yoshida H, Kubo M, Yoshimura A (2002) SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity 17:583-591
46. Kobayashi K, Hernandez LD, Galan JE, Janeway CA Jr, Medzhitov R, Flavell RA (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110:191-202
47. Kobayashi NR, Fan DP, Giehl KM, Bedard AM, Wiegand SJ, Tetzlaff W (1997) BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 17:9583-9595
48. Laflamme N, Echchannaoui H, Landmann R, Rivest S (2003) Cooperation between toll-like receptor 2 and 4 in the brain of mice challenged with cell wall components derived from gram-negative and gram-positive bacteria. Eur J Immunol 33:1127-1138
49. Laflamme N, Rivest S (2001) Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J 15:155-163
50. Laflamme N, Soucy G, Rivest S (2001) Circulating cell wall components derived from gram-negative, not gram-positive, bacteria cause a profound induction of the gene-encoding Tolllike receptor 2 in the CNS. J Neurochem 79:648-657
51. Lafon M, Megret F, Lafage M, Prehaud C (2006) The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA. J Mol Neurosci 29:185-194
52. Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, Rosenberg PA, Volpe JJ, Vartanian T (2002) The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci 22:2478-2486
53. Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T (2003) Activation of innate immunity in the CNS triggers neurodegeneration through a Tolllike receptor 4-dependent pathway. Proc Natl Acad Sci USA 100:8514-8519
54. Lehnardt S, Schott E, Trimbuch T, Laubisch D, Krueger C, Wulczyn G, Nitsch R, Weber JR (2008) A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. J Neurosci 28:2320-2331
55. Li L, Lu J, Tay SS, Moochhala SM, He BP (2007) The function of microglia, either neuroprotec-tion or neurotoxicity, is determined by the equilibrium among factors released from activated microglia in vitro. Brain Res 1159:8-17
56. Li M, Carpio DF, Zheng Y, Bruzzo P, Singh V, Ouaaz F, Medzhitov RM, Beg AA (2001) An essential role of the NF-kappa B/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells. J Immunol 166:7128-7135
57. Liew FY, Xu D, Brint EK, O'Neill LA (2005) Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immunol 5:446-458
58. Ma Y, Li J, Chiu I, Wang Y, Sloane JA, Lu J, Kosaras B, Sidman RL, Volpe JJ, Vartanian T (2006) Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neu-ronal apoptosis. J Cell Biol 175:209-215
59. Mabon PJ, Weaver LC, Dekaban GA (2000) Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment. Exp Neurol 166:52-64
60. Maslinska D, Laure-Kamionowska M, Maslinski S (2004) Toll-like receptors in rat brains injured by hypoxic-ischaemia or exposed to staphylococcal alpha-toxin. Folia Neuropathol 42:125-132
61. Mautes AE, Noble LJ (2000) Co-induction of HSP70 and heme oxygenase-1 in macrophages and glia after spinal cord contusion in the rat. Brain Res 883(2):233-237
62. McTigue DM, Horner PJ, Stokes BT, Gage FH (1998) Neurotrophin-3 and brain-derived neu-rotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J Neurosci 18:5354-5365
63. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135-145
64. Nakagawa R, Naka T, Tsutsui H, Fujimoto M, Kimura A, Abe T, Seki E, Sato S, Takeuchi O, Takeda K, Akira S, Yamanishi K, Kawase I, Nakanishi K, Kishimoto T (2002) SOCS-1 participates in negative regulation of LPS responses. Immunity 17:677-687
65. Nesic O, Xu GY, McAdoo D, High KW, Hulsebosch C, Perez-Pol R (2001) IL-1 receptor antagonist prevents apoptosis and caspase-3 activation after spinal cord injury. J Neurotrauma 18:947-956
66. Nguyen MD, Julien JP, Rivest S (2002) Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci 3:216-227
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. Okamura Y, Watari M, Jerud ES, Young DW, Ishizaka ST, Rose J, Chow JC, Strauss JF 3rd (2001) The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem 276:10229-10233
69. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 97:13766-13771
70. Perry VH, Brown MC, Gordon S (1987) The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration. J Exp Med 165:1218-1223
71. Piani D, Fontana A (1994) Involvement of the cystine transport system xc-in the macrophage-induced glutamate-dependent cytotoxicity to neurons. J Immunol 152:3578-3585
72. Popovich PG, Guan Z, McGaughy V, Fisher L, Hickey WF, Basso DM (2002) The neuropatho-logical and behavioral consequences of intraspinal microglial/macrophage activation. J Neuropathol Exp Neurol 61:623-633
73. Popovich PG, Guan Z, Wei P, Huitinga I, van Rooijen N, Stokes BT (1999) Depletion of hematog-enous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol 158:351-365
74. Popovich PG, Hickey WF (2001) Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord. J Neuropathol Exp Neurol 60:676-685
75. Popovich PG, Wei P, Stokes BT (1997) The cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol 377:443-464
76. Prasad D, Schiff D (2005) Malignant spinal-cord compression. Lancet Oncol 6:15-24
77. Reddy RC, Chen GH, Tekchandani PK, Standiford TJ (2001) Sepsis-induced immunosuppres-sion: from bad to worse. Immunol Res 24:273-287
78. Rolls A, Shechter R, London A, Ziv Y, Ronen A, Levy R, Schwartz M (2007) Toll-like receptors modulate adult hippocampal neurogenesis. Nat Cell Biol 9:1081-1088
79. Rosenberg LJ, Wrathall JR (1997) Quantitative analysis of acute axonal pathology in experimental spinal cord contusion. J Neurotrauma 14:823-838
80. Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, Dumitriu IE, Muller S, Iannacone M, Traversari C, Bianchi ME, Manfredi AA (2004) HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 5:825-830
81. Satake K, Matsuyama Y, Kamiya M, Kawakami H, Iwata H, Adachi K, Kiuchi K (2000) Nitric oxide via macrophage iNOS induces apoptosis following traumatic spinal cord injury. Brain Res Mol Brain Res 85:114-122
82. Schonberg DL, Popovich PG, McTigue DM (2007) Oligodendrocyte generation is differentially influenced by Toll-like receptor (TLR) 2 and TLR4-mediated intraspinal macrophage activation. J Neuropathol Exp Neurol 66:1124-1135
83. Sekhon LH, Fehlings MG (2001) Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 26:S2-S12
84. Shedid D, Benzel EC (2007) Cervical spondylosis anatomy: pathophysiology and biomechanics. Neurosurgery 60:S7-S13
85. Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146-156
86. Sroga JM, Jones TB, Kigerl KA, McGaughy VM, Popovich PG (2003) Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol 462:223-240
87. Struve J, Maher PC, Li YQ, Kinney S, Fehlings MG, Kuntz C, Sherman LS (2005) Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferation. Glia 52:16-24
88. Su Y, Zhang Z, Trautmann K, Xu S, Schluesener HJ (2005) TLR and NOD2 ligands induce cell proliferation in the rat intact spinal cord. J Neuropathol Exp Neurol 64:991-997
89. Taguchi T, Mitcham JL, Dower SK, Sims JE, Testa JR (1996) Chromosomal localization of TIL, a gene encoding a protein related to the Drosophila transmembrane receptor Toll, to human chromosome 4p14. Genomics 32:486-488
90. Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, Lathia JD, Siler DA, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson MP (2007) Pivotal role for neuronal Tolllike receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci USA 104:13798-13803
91. Tanga FY, Nutile-McMenemy N, DeLeo JA (2005) The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci USA 102:5856-5861
92. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC (2002) Oligosaccharides of hyaluronan activate dendritic cells via tolllike receptor 4. J Exp Med 195:99-111
93. Thuret S, Moon LD, Gage FH (2006) Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 7:628-643
94. Triantafilou M, Gamper FG, Haston RM, Mouratis MA, Morath S, Hartung T, Triantafilou K (2006) Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol Chem 281:31002-31011
95. Underhill DM, Ozinsky A, Hajjar AM, Stevens A, Wilson CB, Bassetti M, Aderem A (1999) The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401:811-815
96. Vallieres N, Berard JL, David S, Lacroix S (2006) Systemic injections of lipopolysaccharide accelerates myelin phagocytosis during Wallerian degeneration in the injured mouse spinal cord. Glia 53:103-113
97. Windle WF, Chambers WW (1950) Regeneration in the spinal cord of the cat and dog. J Comp Neurol 93:241-257
98. Ye JH, Houle JD (1997) Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol 143:70-81
99. Yin Y, Cui Q, Li Y, Irwin N, Fischer D, Harvey AR, Benowitz LI (2003) Macrophage-derived factors stimulate optic nerve regeneration. J Neurosci 23:2284-2293
100. Yin Y, Henzl MT, Lorber B, Nakazawa T, Thomas TT, Jiang F, Langer R, Benowitz LI (2006) Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat Neurosci 9:843-852
101. Yu M, Wang H, Ding A, Golenbock DT, Latz E, Czura CJ, Fenton MJ, Tracey KJ, Yang H (2006) HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock 26:174-179
102. Yune TY, Chang MJ, Kim SJ, Lee YB, Shin SW, Rhim H, Kim YC, Shin ML, Oh YJ, Han CT, Markelonis GJ, Oh TH (2003) Increased production of tumor necrosis factor-alpha induces apoptosis after traumatic spinal cord injury in rats. J Neurotrauma 20:207-219
103. Zekki H, Feinstein DL, Rivest S (2002) The clinical course of experimental autoimmune encepha-lomyelitis is associated with a profound and sustained transcriptional activation of the genes encoding toll-like receptor 2 and CD14 in the mouse CNS. Brain Pathol 12:308-319
104. Zhang G, Ghosh S (2002) Negative regulation of toll-like receptor-mediated signaling by Tollip. J Biol Chem 277:7059-7065
105. Zhang Z, Schluesener HJ (2006) Mammalian toll-like receptors: from endogenous ligands to tissue regeneration. Cell Mol Life Sci 63:2901-2907
106. Zhang Z, Trautmann K, Schluesener HJ (2005) Microglia activation in rat spinal cord by systemic injection of TLR3 and TLR7/8 agonists. J Neuroimmunol 164:154-160