Glial reaction in Parkinson's diseases: Inflammatory activation signaling of glia as a potential therapeutic target

Current Signal Transduction Therapy

Volumn 2, Issue 1, 2007, Pages 77-90

  Choi, Dong Kug ^a   Suk, Kyoungho ^b  

^a Konkuk University   (South Korea)

^b Kyungpook National University School of Medicine   (South Korea)

Author keywords

Astrocyte; Central nervous system; Experimental animal model; Microglia; Minocycline; Neurodegenerative diseases; Neuroinflammation; Parkinson's disease; Signal transduction

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; ANTIINFLAMMATORY AGENT; BASIC FIBROBLAST GROWTH FACTOR; CYCLOOXYGENASE 2 INHIBITOR; CYTOKINE; DEXAMETHASONE; DOPAMINE; EPIDERMAL GROWTH FACTOR; INDUCIBLE NITRIC OXIDE SYNTHASE; LEVODOPA; MINOCYCLINE; MITOGEN ACTIVATED PROTEIN KINASE; NEUROTOXIN; PROSTAGLANDIN; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SALICYLATE SODIUM; STAT1 PROTEIN; STROMELYSIN; TETRACYCLINE DERIVATIVE; TOLL LIKE RECEPTOR; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA1; WOGONIN;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; ASTROCYTOSIS; AUTOPSY; BRAIN INJURY; CELL ACTIVATION; CENTRAL NERVOUS SYSTEM DISEASE; CYTOKINE RELEASE; DISEASE ASSOCIATION; DOPAMINERGIC NERVE CELL; DRUG TARGETING; ENCEPHALITIS; EXPERIMENTAL ANIMAL; GLIA CELL; HUMAN; INFLAMMATORY DISEASE; INTRACELLULAR SPACE; MICROGLIA; MOLECULAR MECHANICS; NERVE CELL DEGENERATION; NERVE CELL INHIBITION; NERVE CELL NECROSIS; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN SYNTHESIS INHIBITION; REVIEW; SIGNAL TRANSDUCTION; SUBSTANTIA NIGRA;

EID: 34248325703     PISSN: 15743624     EISSN: None     Source Type: Journal    
DOI: 10.2174/157436207779317146     Document Type: Review

References (141)

1. Olson EE, McKeon RJ. Characterization of cellular and neurological damage following unilateral hypoxia/ischemia. J Neurol Sci 2004; 227: 7-19.
2. Morioka T, kalehua AN, Streit WJ. Characterization of microglial reaction after middle cerebral artery occlusion in rat brain. J. Comp. Neurol 1993; 327: 123-132.
3. Tsuda M, Mizokoshi A, Shigemoto-Mogami Y, Koizumi S, Iniue K. Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. Glia 2004; 45: 89-95.
4. Liu B, Hong JS. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 2003; 304: 1-7.
5. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19: 312-318.
6. Akiyama H, Barger S, Barnum S, et al., Inflammation and Alzheimer's disease. Neurobiol Aging 2000; 21: 383-421.
7. Rogers J, Luber-Narod J, Styren SD, Civin WH. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer's disease. Neurobiol Aging 1988; 9: 339-49.
8. Forman MS, Trojanowski JQ, Lee VM. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 2004; 10: 1055-1063.
9. McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 1988; 38: 1285-1291.
10. Mogi M, Harada M, Kondo T, Riederer P, Nagatsu T. Brain beta 2-microglobulin levels are elevated in the striatum in Parkinson's disease. J Neural Transm Park Dis Dement Sect 1995; 9: 87-92.
11. Fahn S, Przedborski S. Parkinsonism in Merritt's neurology. Lippincott Williams & Wilkins, New York 2000; 679-693.
12. Rascol O, Payoux P, Ory F, Ferreira JJ, Brefel-Courbon C, Montastruc JL. Limitations of current Parkinson's disease therapy. Ann Neurol 2003; 53(Suppl 3): S3-12; discussion S12-5.
13. Greenamyre JT, MacKenzie G, Peng TI, Stephans SE. Mitochondrial dysfunction in Parkinson's disease. Biochem Soc Symp 1999; 66: 85-97.
14. Forno LS, De Lanney LE, Irwin I, Di Monte D, Langston JW. Astrocytes and Parkinson's disease. Prog Brain Res 1992; 94: 429-436.
15. Banati RB, Daniel SE, Blunt SB. Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease. Mov Disord 1998; 13: 221-227.
16. Mirza B, Hadberg H, Thomsen P, Moos T. The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease. Neuroscience 2000; 95: 425-432.
17. Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 1994; 165: 208-210.
18. Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl 2000; 60: 277-290.
19. Bessler H, Djaldetti R, Salman H, Bergman M, Djaldetti M. IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson's disease. Biomed Pharmacother 1999; 53: 141-145.
20. Boka G, Anglade P, Wallach D, Javoy-Agid F, Agid Y, Hirsch EC. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease. Neurosci Lett 1994; 172: 151-154.
21. Hunot S, Dugas N, Faucheux B, et al. Fc RII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci 1999; 19: 3440-3447.
22. Peterson PK, Hu S, Anderson WR, Chao CC. Nitric oxide production and neurotoxicity mediated by activated microglia from human versus mouse brain. J Infect Dis 1994; 170: 457-460.
23. -) regulatory pathways. J Immunol 1996; 157: 2129-2135.
24. Liu J, Zhao ML, Brosnan CF, Lee SC. Expression of type II nitric oxide synthase in primary human astrocytes and microglia: role of IL-1beta and IL-1 receptor antagonist. J Immunol 1996; 157: 3569-3676.
25. Ding M, St Pierre BA, Parkinson JF, et al. Inducible nitric-oxide synthase and nitric oxide production in human fetal astrocytes and microglia. A kinetic analysis. J Biol Chem 1997; 272: 11327-11335.
26. Langston JW, Irwin I. MPTP: current concepts and controversies. Clin Neuropharmacol 1986; 9: 485-507.
27. Seniuk NA, Tatton WG, Greenwood CE. Dose-dependent destruction of the coeruleus-cortical and nigral-striatal projections by MPTP. Brain Res 1990; 527: 7-20.
28. Muthane U, Ramsay KA, Jiang H, et al. Differences in nigral neuron number and sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57/b1 and CD-1mice. Exp Neurol 1994; 126: 195-204.
29. Moratalla R, Quinn B, DeLanney LE, Irwin I, Langston JW, Graybiel AM. Differential vulnerability of primate caudate-putamen and striosome-matrix dopamine systems to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 1992; 89: 3859-3863.
30. Forno LS, Langston JW, DeLanney LE, Irwin I, Ricaurte GA. Locus coeruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann Neurol 1986; 20: 449-455.
31. Meredith GE, Totterdell S, Dervan AG, Lau YS. Alpha synuclein inclusions are associated with a persistent microglial reaction in a chronic mouse model of Parkinson's disease. Society for Neuroscience, Washington DC 2002; online program No 386.12.
32. DiMauro S. Mitochondrial involvement in Parkinson's disease: the controversy continues. Neurology 1993; 43: 2170-2172.
33. Nicklas WJ, Yougster SK, Kindt MV, Heikkila RE. MPTP, MPP+ and mitochondrial function. Life Sci 1987; 40: 721-729.
34. Sachs C, Jonsson G. Mechanisms of action of 6-hydroxydopamine. Biochem Pharmacol 1975; 24: 1-8.
35. Czlonkowska A, Kohutnicka M, Kurkowska-Jastrzebska I, Czlonkowski A. Microglial reaction in MPTP (1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine) induced Parkinson's disease mice model. Neurodegeneration 1996; 5: 137-143.
36. Kohutnicka M, Lewandowska E, Kurkowska-Jastrzebska I, Czlonkowski A, Czlonkowska A. Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunopharmacology 1998; 39: 167-180.
37. Liberatore GT, Jackson-Lewis V, Vukosavic S, et al. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. Nat Med 1999; 5: 1403-1409.
38. Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz JB. Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem 2000; 74: 2213-2216.
39. Akiyama H, McGeer PL. Microglial response to 6-hydroxydopamine-induced substantia nigra lesions. Brain Res 1989; 489: 247-253.
40. Cicchetti F, Brownell AL, Williams K, Chen YI, Livni E, Isacson O. Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 2002; 15: 991-998.
41. Betarbet R, Sherer TB, MacKenzie G, et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 2000; 12: 1301-1306.
42. Gao HM, Hong JS, Zhang W, Liu B. Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 2002; 22:782-790.
43. Gao HM, Hong JS, Zhang W, Liu B. Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinsons disease. J Neurosci 2003; 23: 1228-36
44. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW. Cytotoxicity of microglia. Glia 1993; 7: 111-118.
45. Babior BM. NADPH oxidase: an update. Blood 1999; 93: 1464-1476.
46. Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 1994; 78: 915-918.
47. Wu DC, Jackson-Lewis V, Vila M, et al. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 2002; 22: 1763-1771.
48. Wu DC, Teismann P, Tieu K, et al. NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci USA 2003; 100: 6145-6150.
49. Pennathur S, Jackson-Lewis V, Przedborski S, Heinecke JW. Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and o,o'-dityrosine in brain tissue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, a model of oxidative stress in Parkinson's disease. J Biol Chem 1999; 274: 34621-34628.
50. Hampton MB, Kettle AJ, Winterbourn CC. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 1998; 92: 3007-3017.
51. Hazen SL, Zhang R, Shen Z, et al. Formation of nitric oxide-derived oxidants by myeloperoxidase in monocytes: pathways for monocyte-mediated protein nitration and lipid peroxidation in vivo. Circ Res 1999; 85: 950-958.
52. Harrison JE, Schultz J. Studies on the chlorinating activity of myeloperoxidase. J Biol Chem 1976; 251: 1371-1374.
53. Choi DK, Pennathur S, Perier C, et al. Ablation of the inflammatory enzyme myeloperoxidase mitigates features of Parkinson's disease in mice. J Neurosci 2005; 28: 6594-600.
54. Gaut JP, Yeh GC, Tran HD, et al. Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis. Proc Natl Acad Sci USA 2001; 98: 11961-11966.
55. Malle E, Hazell L, Stocker R, Sattler W, Esterbauer H, Waeg G. Immunologic detection and measurement of hypochlorite-modified LDL with specific monoclonal antibodies. Arterioscler Thromb Vasc Biol 1995; 15: 982-989.
56. Gehrmann J, Matsumoto Y, Kreutzberg GW. Microglia: intrinsic immuneffector cell of the brain. Brain Res Brain Res Rev 1995; 20: 269-287.
57. Gremo F, Sogos V, Ennas MG, et al. Features and functions of human microglia cells. Adv Exp Med Biol 1997; 429: 79-97.
58. Stoll G, Jander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 1999; 58: 233-247.
59. Streit WJ, Walter SA, Pennell NA. Reactive microgliosis. Prog Neurobiol 1999; 57: 563-581.
60. Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog Neurobiol 1998; 54: 99-125.
61. Gonzalez-Scarano F, Baltuch G. Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 1999; 22: 219-240.
62. Araque A, Perea G. Glial modulation of synaptic transmission in culture. Glia 2004; 47: 241-248.
63. Aschner M. Astrocytes as mediators of immune and inflammatory responses in the CNS. Neurotoxicology 1998; 19: 269-281.
64. Vesce S, Bezzi P, Volterra A. The active role of astrocytes in synaptic transmission. Cell Mol Life Sci 1999; 56: 991-1000.
65. Sawada M, Kondo N, Suzumura A, Marunouchi T. Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res 1989; 491: 394-397.
66. Galea E, Feinstein DL, Reis DJ. Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures. Proc Natl Acad Sci USA 1992; 89: 10945-10949.
67. Simmons ML, Murphy S. Induction of nitric oxide synthase in glial cells. J Neurochem 1992; 59: 897-905.
68. Becher B, Prat A, Antel JP. Brain-immune connection: immunoregulatory properties of CNS-resident cells. Glia 2000; 29: 293-304.
69. Chong ZZ, Li F, Maiese K. Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease. Brain Res Brain Res Rev 2005; 49: 1-21.
70. Nakamura Y. Regulating factors for microglial activation. Biol Pharm Bull 2002; 25: 945-953.
71. Ambrosi G, Virgintino D, Benagiano V, Maiorano E, Bertossi M, Roncali L. Glial cells and blood-brain barrier in the human cerebral cortex. Ital J Anat Embryol 1995; 100(Suppl 1): 177-184.
72. Hansson E, Ronnback L. Glial neuronal signaling in the central nervous system. FASEB J 2003; 17: 341-348.
73. Henson PM, Johnston RB, Jr. Tissue injury in inflammation. Oxidants, proteinases, and cationic proteins. J Clin Invest 1987; 79: 669-674.
74. Ward PA, Warren JS, Johnson KJ. Oxygen radicals, inflammation, and tissue injury. Free Radic Biol Med 1988; 5: 403-408.
75. Rankin JA. Biological mediators of acute inflammation. AACN Clin Issues 2004; 15: 3-17.
76. Halliwell B. Oxygen radicals, nitric oxide and human inflammatory joint disease. Ann Rheum Dis 1995; 54: 505-510.
77. Nakajima K, Kohsaka S. Microglia: activation and their significance in the central nervous system. J Biochem (Tokyo) 2001; 130: 169-175.
78. Chavarria A, Alcocer-Varela J. Is damage in central nervous system due to inflammation? Autoimmun Rev 2004; 3: 251-260.
79. Streit WJ, Mrak RE, Griffin WS. Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation 2004; 1: 14.
80. Streit WJ. Microglia as neuroprotective, immunocompetent cells of the CNS. Glia 2002; 40: 133-139.
81. Popovich PG, Jones TB. Manipulating neuroinflammatory reactions in the injured spinal cord: back to basics. Trends Pharmacol Sci 2003; 24: 13-17.
82. Kim YS, Kim SS, Cho JJ, et al. Matrix metalloproteinase-3: a novel signaling proteinase from apoptotic neuronal cells that activates microglia. J Neurosci 2005; 25: 3701-3711.
83. Da Silva J, Pierrat B, Mary JL, Lesslauer W. Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes. J Biol Chem 1997; 272: 28373-28380.
84. Bhat NF, Zhang P, Lee JC, Hogan EL. Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-alpha gene expression in endotoxin-stimulated primary glial cultures. J Neurosci 1998; 18: 1633-1641.
85. Xu X, Malave A. P38 MAPK, but not p42/p44 MAPK mediated inducible nitric oxide synthase expression in C6 glioma cells. Life Sci 2000; 67: 3221-3230.
86. Won J, Lee J, Suh H. Forskolin inhibits expression of inducible nitric oxide synthase mRNA via inhibiting the mitogen activated protein kinase in C6 cells. Brain Res Mol Brain Res 2001; 89: 1-10.
87. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410: 37-40.
88. Kyriakis JM, Banerjee P, Nikolakaki E, et al. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 1994; 369: 156-160.
89. Lee JC, Laydon JT, McDonnell PC, et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 1994; 372: 739-746.
90. Lee J, Hur J, Lee P, et al. Dual role of inflammatory stimuli in activation-induced cell death of mouse microglial cells: initiation of two separate apoptotic pathways via induction of interferon regulatory factor-1 and caspase-11. J Biol Chem 2001; 276: 32956-32965.
91. Watters JJ, Sommer JA, Pfeiffer ZA, Prabhu U, Guerra AN, Bertics PJ. A differential role for the mitogen-activated protein kinases in lipopolysaccharide signaling: the MEK/ERK pathway is not essential for nitric oxide and interleukin 1beta production. J Biol Chem 2002; 277: 9077-9087.
92. Lee H, Suk K. Selective modulation of microglial signal transduction by PACAP. Neuroreport 2004; 15: 1469-1474.
93. Park SY, Lee H, Hur J, et al. Hypoxia induces nitric oxide production in mouse microglia via p38 mitogen-activated protein kinase pathway. Brain Res Mol Brain Res 2002; 107: 9-16.
94. Guan Z, Baier LD, Morrison AR. p38 mitogen-activated protein kinase down-regulates nitric oxide and up-regulates prostaglandin E2 biosynthesis stimulated by interleukin-1beta. J Biol Chem 1997; 272: 8083-8089.
95. Nishiya T, Uehara T, Edamatsu H, Kaziro Y, Itoh H, Nomura Y. Activation of Statl and subsequent transcription of inducible nitric oxide synthase gene in C6 glioma cells is independent of interferon-gamma-induced MAPK activation that is mediated by p21ras. FEBS Lett 1997; 408: 33-38.
96. Chandel NS, Trzyna WC, McClintock DS, Schumacker PT. Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin. J Immumol 2000; 165: 1013-1021.
97. Kunz M, Ibrahim S, Koczan D, et al. Activation of c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) is critical for hypoxia-induced apoptosis of human malignant melanoma. Cell Growth Differ 2001; 12: 137-145.
98. Yin K, Juurlink BH. Regulation of expression of nuclear factor kappa B Re1A in oligodendrocytes: effect of hypoxia. Neuroreport 2000; 11: 1877-1881.
99. Boehm U, Klamp T, Groot M, Howard JC. Cellular responses to interferon-gamma. Annu Rev Immunol 1997; 15: 749-795.
100. Suk K, Chang I, Kim YH, et al. Interferon gamma (IFN-gamma) and tumor necrosis factor alpha synergism in ME-180 cervical cancer cell apoptosis and necrosis. IFN-gamma inhibits cytoprotective NF-kappa B through STAT1/IRF-1 Pathways. J Biol Chem 2001; 276: 13153-13159.
101. Lee P, Lee J, Kim S, et al. NO as an autocrine mediator in the apoptosis of activated microglial cells: correlation between activation and apoptosis of microglial cells. Brain Res 2001; 892: 380-385.
102. Lee H, Cha S, Lee MS, Cho GJ, Choi WS, Suk K. Role of antiproliferative B cell translocation gene-1 as an apoptotic sensitizer in activation-induced cell death of brain microglia. J Immunol 2003; 171: 5802-5811.
103. Aliprantis AO, Yang RB, Mark MR, et al. Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science 1999; 285: 736-739.
104. Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature 2004; 430: 257-263.
105. Hsu LC, Park JM, Zhang K, et al. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 2004; 428: 341-345.
106. Into T, Kiura K, Yasuda M, et al. Stimulation of human Toll-like receptor (TLR) 2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-kappa B activation. Cell Microbiol 2004; 6: 187-199.
107. Ruckdeschel K, Pfaffinger G, Haase R, et al. Signaling of apoptosis through TLRs critically involves toll/IL-1 receptor domain-containing adapter inducing IFN-beta, but not MyD88, in bacteria-infected murine macrophages. J Immunol 2004; 173: 3320-3328.
108. Jung DY, Lee H, Jung BY, et al. TLR4, but not TLR2, signals autoregulatory apoptosis of cultured microglia: a critical role of IFN-beta as a decision maker. J Immunol 2005; 174: 6467-6476.
109. Yoneyama M, Suhara W, Fukuhara Y, Fukuda M, Nishida E, Fujita T. Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/ p300. EMBO J 1998; 17: 1087-1095.
110. Iwamura T, Yoneyama M, Yamaguchi K, et al. Induction of IRF-3/7 kinase and NF-kappaB in response to double-stranded RNA and virus infection: common and unique pathways. Genes Cells 2001; 6: 375-388.
111. Park EJ, Park SY, Joe EH, Jon I 15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia. J Biol Chem 2003; 278: 14747-14752.
112. Toshchakov V, Jones BW, Perera PY, et al. TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages. Nat Immunol 2002; 3: 392-398.
113. Ryu J, Pyo H, Jou I, Joe E. Thrombin induces NO release from cultured rat microglia via protein kinase C, mitogen-activated protein kinase, and NF-kappa B. J Biol Chem 2000; 275: 29955-29959.
114. Kingham PJ, Cuzner ML, Pocock JM. Apoptotic pathways mobilized in microglia and neurones as a consequence of chromogranin A-induced microglial activation. J Neurochem 1999; 73: 538-547.
115. Pyo H, Joe E, Jung S, Lee SH, Jou I. Gangliosides activate cultured rat brain microglia. J Biol Chem 1999; 274: 34584-34589.
116. Meda L, Cassatella MA, Szendrei GI, et al. Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature 1995; 374: 647-650.
117. Kim OS, Park EJ, Joe EH, Jou I. JAK-STAT signaling mediates gangliosides-induced inflammatory responses in brain microglial cells. J Biol Chem 2002; 277: 40594-40601.
118. Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem 2002; 71: 635-700.
119. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4: 499-511.
120. Kim SJ, Sung JY, Um JW, et al. Parkin cleaves intracellular alpha-synuclein inclusions via the activation of calpain. J Biol Chem 2003; 278: 41890-41899.
121. Sung JY, Park SM, Lee CH, et al. Proteolytic cleavage of extracellular secreted alpha-synuclein via matrix metalloproteinases. J Biol Chem 2005; 280: 25216-25224.
122. Gan HM, Liu B, Zhang W, Hong JS. Novel anti-inflammatory therapy for Parkinson's disease. Trends Pharmacol Sci 2003; 24: 395-401.
123. Hanisch UK. Microglia as a source and target of cytokines. Glia 2002; 40: 140-155.
124. McGeer PL, McGeer EG. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 1995; 21: 195-218.
125. Lee H, Kim YO, Kim SY, et al. Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J 2003; 17: 1943-1944.
126. Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships. Biochem Pharmacol 1999; 58: 759-765.
127. Wakabayashi I. Inhibitory effects of baicalein and wogonin on lipopolysaccharide- induced nitric oxide production in macrophages. Pharmacol Toxicol 1999; 84: 288-291.
128. Wakabayashi I, Yasui K. Wogonin inhibits inducible prostaglandin E(2) production in macrophages (In Process Citation). Eur J Pharmacol 2000; 406: 477-481.
129. Chang YL, Shen JJ, Wung BS, Cheng JJ, Wang DL. Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells. Mol Pharmacol 2001; 60: 507-513.
130. Park BK, Hen MY, Park H, Kim HP. Inhibition of TPA-induced cyclooxygenase-2 expression and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix. Eur J Pharmacol 2001; 425: 153-157.
131. Kandaswami C, Middleton E, Jr. Free radical scavenging and antioxidant activity of plant flavonoids. Adv Exp Med Biol 1994; 366: 351-376.
132. Gan Z, Huang K, Yang X, Xu H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1999; 1472: 643-650.
133. Shieh DE, Liu LT, Lin CC. Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin (In Process Citation). Anticancer Res 2000; 20: 2861-2865.
134. Kim H, Kim YS, Kim SY, Suk K. The plant flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production. Neurosci Lett 2001; 309: 67-71.
135. Rifkin BR, Vemillo AT, Golub LM, Ramamurthy NS. Modulation of bone resorption by tetracyclines. Ann N Y Acad Sci 1994; 732: 165-180.
136. Amin AR, Attur MG, Thakker GD, et al. A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. Proc Natl Acad Sci USA 1996; 93: 14014-14019.
137. Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998; 95: 15769-15774.
138. Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 1999; 96: 13496-13500.
139. Tikka T, Fiebich BL, Goldsteins G, Keinanen F, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 2001; 21: 2580-2588.
140. Tikka TM, Koistinaho JE. Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia. J Immunol 2001; 166: 7527-7533.
141. Suk K. Minocycline suppresses hypoxic activation of rodent microglia in culture. Neurosci Lett 2004; 366: 167-171.