Targeting the peroxisome proliferator-activated receptors (PPARs) in spinal cord injury

Expert Opinion on Therapeutic Targets

Volumn 15, Issue 8, 2011, Pages 943-959

  Esposito, Emanuela ^a,b   Cuzzocrea, Salvatore ^a,b  

^a UNIVERSITY OF MESSINA   (Italy)

^b IRCCS CENTRO NEUROLESI BONINO PULEJO   (Italy)

Author keywords

Peroxisome proliferator activated receptors; Spinal cord injury

Indexed keywords

2 [4 [2 [3 (2,4 DIFLUOROPHENYL) 1 HEPTYLUREIDO]ETHYL]PHENYLTHIO] 2 METHYLPROPIONIC ACID; 2 [4 [2 [3 CYCLOHEXYL 1 (4 CYCLOHEXYLBUTYL)UREIDO]ETHYL]PHENYLTHIO] 2 METHYLPROPIONIC ACID; 2 [4 [3 [4,5 DIHYDRO 1 (4 METHYLBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 3 YL]PROPYL]PHENOXY] 2 METHYLPROPIONIC ACID; 3 CHLORO 4 [3 (7 PROPYL 3 TRIFLUOROMETHYLBENZISOXAZOL 6 YLOXY)PROPYLTHIO]PHENYLACETIC ACID; 4 [4 [3 (4 ACETYL 3 HYDROXY 2 PROPYLPHENOXY)PROPOXY]PHENOXY]ACETIC ACID; 5 (2,4 DIOXO 5 THIAZOLIDINYLMETHYL) 2 METHOXY N [4 (TRIFLUOROMETHYL)BENZYL]BENZAMIDE; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID; [4 [2 (3 FLUORO 4 TRIFLUOROMETHYLPHENYL) 4 METHYL 5 THIAZOLYLMETHYLTHIO] 2 METHYLPHENOXY]ACETIC ACID; AD 5061; DRF 2519; FENOFIBRIC ACID; GLITAZONE DERIVATIVE; GW 409544; IMIGLITAZAR; L 796449; LY 465608; LY 510929; METHYLPREDNISOLONE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; RAGAGLITAZAR; SB 219994; TZD 18; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; CENTRAL NERVOUS SYSTEM; DEGENERATIVE DISEASE; DRUG MEGADOSE; DRUG SAFETY; DRUG TARGETING; HUMAN; IMMUNOMODULATION; NEUROPROTECTION; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SPINAL CORD DECOMPRESSION; SPINAL CORD INJURY;

HUMANS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; SPINAL CORD INJURIES;

EID: 79960237311     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2011.581231     Document Type: Review

References (150)

1. National Spinal Cord Injury Statistical Center. Spinal cord injury facts and figures at a glance. J Spinal Cord Med 2010;33(4):439-40
2. Kwon BK, Sekhon LH, Fehlings MG. Emerging repair, regeneration, and translational research advances for spinal cord injury. Spine 2010;35(21 Suppl):S263-70
3. Lim G, Wang S, Zeng Q, et al. Spinal glucocorticoid receptors contribute to the development of morphine tolerance in rats. Anesthesiology 2005;102:832-7 (Pubitemid 40462864)
4. Hurlbert RJ. Strategies of medical intervention in the management of acute spinal cord injury. Spine 2006;31(11 Suppl):S16-21; discussion S36
5. Cuzzocrea S. Peroxisome proliferator-activated receptors and acute lung injury. Curr Opin Pharmacol 2006;6:263-70
6. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004;351:1106-18
7. Israelian-Konaraki Z, Reaven PD. Peroxisome proliferator-activated receptor-alpha and atherosclerosis: from basic mechanisms to clinical implications. Cardiology 2005;103:1-9 (Pubitemid 39541239)
8. Lee CH, Olson P, Hevener A, et al. PPARDelta regulates glucose metabolism and insulin sensitivity. Proc Natl Acad Sci USA 2006;103:3444-9 (Pubitemid 43346488)
9. Kilgore KS, Billin AN. PPARbeta/delta ligands as modulators of the inflammatory response. Curr Opin Investig Drugs 2008;9:463-9 (Pubitemid 351677899)
10. Popovich PG, Stuckman S, Gienapp IE, Whitacre CC. Alterations in immune cell phenotype and function after experimental spinal cord injury. J Neurotrauma 2001;18:957-66 (Pubitemid 32852895)
11. Dusart I, Schwab ME. Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J Neurosci 1994;6:712-24 (Pubitemid 24143919)
12. Popovich PG, Wei P, Stokes BT. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol 1997;377:443-64 (Pubitemid 27016650)
13. Ahn YH, Lee G, Kang SK. Molecular insights of the injured lesions of rat spinal cords: Inflammation, apoptosis, and cell survival. Biochem Biophys Res Commun 2006;348:560-70 (Pubitemid 44188602)
14. Gonzalez R, Glaser J, Liu MT, et al. Reducing inflammation decreases secondary degeneration and functional deficit after spinal cord injury. Exp Neurol 2003;184:456-63 (Pubitemid 37444053)
15. Bartholdi D, Schwab ME. Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: an in situ hybridization study. Eur J Neurosci 1997;9:1422-38 (Pubitemid 27303243)
16. Glaser J, Gonzalez R, Perreau VM, et al. Neutralization of the chemokine CXCL10 enhances tissue sparing and angiogenesis following spinal cord injury. J Neurosci Res 2004;77:701-8 (Pubitemid 39194611)
17. Rice T, Larsen J, Rivest S, Yong VW. Characterization of the early neuroinflammation after spinal cord injury in mice. J Neuropathol Exp Neurol 2007;66:184-95 (Pubitemid 46673274)
18. Hu R, Zhou J, Luo C, et al. Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury. J Neurosurg Spine 2010;13:169-80
19. Beck KD, Nguyen HX, Galvan MD, et al. Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain 2010;133:433-47
20. Schnell L, Fearn S, Klassen H, et al. Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord. Eur J Neurosci 1999;11:3648-58 (Pubitemid 29484261)
21. Pollard ME, Apple DF. Factors associated with improved neurologic outcomes in patients with incomplete tetraplegia. Spine 2003;28:33-9
22. Hall ED, Springer JE. Neuroprotection and acute spinal cord injury: a reappraisal. NeuroRx 2004;1:80-100 (Pubitemid 46589342)
23. Amar AP, Levy ML. Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery 1999;44:1027-39; discussion 1039-1040
24. Bracken MB, Collins WF, Freeman DF, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA 1984;251:45-52 (Pubitemid 14212880)
25. Bracken MB, Shepard MJ, Holford TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the third national acute spinal cord injury randomized controlled trial. National Acute Spinal Cord Injury Study. JAMA 1997;277:1597-604 (Pubitemid 27231191)
26. Bracken MB, Shepard MJ, Holford TR, et al. Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury randomized controlled trial. J Neurosurg 1998;89:699-706 (Pubitemid 28485526)
27. Fehlings MG. Editorial: recommendations regarding the use of methylprednisolone in acute spinal cord injury: making sense out of the controversy. Spine 2001;26(24 Suppl):S56-7 (Pubitemid 34019780)
28. Gorio A, Gokmen N, Erbayraktar S, et al. Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci USA 2002;99:9450-5 (Pubitemid 34764634)
29. King VR, Averill SA, Hewazy D, et al. Erythropoietin and carbamylated erythropoietin are neuroprotective following spinal cord hemisection in the rat. Eur J Neurosci 2007;26:90-100 (Pubitemid 47035440)
30. Stahel PF, Barnum SR. The role of the complement system in CNS inflammatory diseases. Expert Rev Clin Immunol 2006;2:445-56 (Pubitemid 44355575)
31. Leinhase I, Rozanski M, Harhausen D, et al. Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice. J Neuroinflammation 2007;4:13
32. Qiao F, Atkinson C, Kindy MS, et al. The alternative and terminal pathways of complement mediate post-traumatic spinal cord inflammation and injury. Am J Pathol 2010;177:3061-70
33. Mortazavi MM, Verma K, Tubbs RS, Theodore N. Cellular and paracellular transplants for spinal cord injury: a review of the literature. Childs Nerv Syst 2011;27:237-43
34. Dadsetan M, Knight AM, Lu L, et al. Stimulation of neurite outgrowth using positively charged hydrogels. Biomaterials 2009;30:3874-81
35. Neville CM, Huang AY, Shyu JY, et al. Neural precursor cell lines promote neurite branching. Int J Neurosci 2009;119:15-39
36. Pellitteri R, Spatuzza M, Russo A, Stanzani S. Olfactory ensheathing cells exert a trophic effect on the hypothalamic neurons in vitro. Neurosci Lett 2007;417:24-9 (Pubitemid 46517836)
37. Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 1993;32:5598-604 (Pubitemid 23178525)
38. Yoshikawa T, Brkanac Z, Dupont BR, et al. Assignment of the human nuclear hormone receptor, NUC1 (PPARD), to chromosome 6p21.1-p21.2. Genomics 1996;35:637-8 (Pubitemid 26271390)
39. Braissant O, Foufelle F, Scotto C, et al. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 1996;137:354-66 (Pubitemid 26005011)
40. Tontonoz P, Hu E, Graves RA, et al. mPPARgamma2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 1994;8:1224-34
41. Braissant O, Wahli W. Differential expression of peroxisome proliferator-activated receptor-alpha, - beta, and -gamma during rat embryonic development. Endocrinology 1998;139:2748-54 (Pubitemid 28512383)
42. Inoue I, Shino K, Noji S, et al. Expression of peroxisome proliferator-activated receptor alpha (PPAR alpha) in primary cultures of human vascular endothelial cells. Biochem Biophys Res Commun 1998;246:370-4 (Pubitemid 28412605)
43. Marx N, Bourcier T, Sukhova GK, et al. PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease. Arterioscler Thromb Vasc Biol 1999;19:546-51 (Pubitemid 29135154)
44. Chinetti G, Griglio S, Antonucci M, et al. Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. J Biol Chem 1998;273:25573-80 (Pubitemid 28475776)
45. Ricote M, Li AC, Willson TM, et al. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998;391:79-82 (Pubitemid 28079218)
46. Marx N, Sukhova G, Murphy C, et al. Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro. Am J Pathol 1998;153:17-23 (Pubitemid 28317502)
47. Chinetti G, Gbaguidi FG, Griglio S, et al. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 2000;101:2411-17 (Pubitemid 30329133)
48. IJpenberg A, Jeannin E, Wahli W, Desvergne B. Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/ retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element. J Biol Chem 1997;272:20108-17 (Pubitemid 27340117)
49. Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002;53:409-35 (Pubitemid 34177889)
50. McKenna NJ, O'Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 2002;108:465-74 (Pubitemid 34260872)
51. Pascual G, Glass CK. Nuclear receptors versus inflammation: mechanisms of transrepression. Trends Endocrinol Metab 2006;17:321-7 (Pubitemid 44397567)
52. Horlein AJ, Naar AM, Heinzel T, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1995;377:397-404
53. Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995;377:454-7
54. Hoberg JE, Yeung F, Mayo MW. SMRT derepression by the IkappaB kinase alpha: a prerequisite to NF-kappaB transcription and survival. Mol Cell 2004;16:245-55 (Pubitemid 39388839)
55. Nolte RT, Wisely GB, Westin S, et al. Ligand binding co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature 1998;395:137-43 (Pubitemid 28425645)
56. Perissi V, Aggarwal A, Glass CK, et al. A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors. Cell 2004;116:511-26 (Pubitemid 38264429)
57. Pascual G, Fong AL, Ogawa S, et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 2005;437:759-63 (Pubitemid 41486547)
58. Lee CH, Chawla A, Urbiztondo N, et al. Transcriptional repression of atherogenic inflammation: modulation by PPARDelta. Science 2003;302:453-7 (Pubitemid 37296272)
59. Chung SW, Kang BY, Kim SH, et al. Oxidized low density lipoprotein inhibits interleukin-12 production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-gamma and nuclear factor-kappaB. J Biol Chem 2000;275:32681-7
60. Ramanan S, Kooshki M, Zhao W, et al. PPARalpha ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-kappaB and AP-1 pathways. Free Radic BiolMed 2008;45:1695-704
61. Alleva DG, Johnson EB, Lio FM, et al. Regulation of murine macrophage proinflammatory and anti-inflammatory cytokines by ligands for peroxisome proliferator-activated receptor-gamma: counter-regulatory activity by IFN-gamma. J Leukoc Biol 2002;71:677-85
62. Zingarelli B, Sheehan M, Hake PW, et al. Peroxisome proliferator activator receptor-gamma ligands, 15-deoxy- Delta12,14-prostaglandin J2 and ciglitazone, reduce systemic inflammation in polymicrobial sepsis by modulation of signal transduction pathways. J Immunol 2003;171:6827-37 (Pubitemid 37532118)
63. Yang XY, Wang LH, Chen T, et al. Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. PPARgamma co-association with transcription factor NFAT. J Biol Chem 2000;275:4541-4 (Pubitemid 30108833)
64. Cunard R, Eto Y, Muljadi JT, et al. Repression of IFN-gamma expression by peroxisome proliferator-activated receptor gamma. J Immunol 2004;172:7530-6 (Pubitemid 38747616)
65. Kelly D, Campbell JI, King TP, et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol 2004;5:104-12 (Pubitemid 38081475)
66. Bishop-Bailey D, Wray J. Peroxisome proliferator-activated receptors: a critical review on endogenous pathways for ligand generation. Prostaglandins Other Lipid Mediat 2003;71:1-22 (Pubitemid 36428519)
67. Cimini A, Benedetti E, Cristiano L, et al. Expression of peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RXRs) in rat cortical neurons. Neuroscience 2005;130:325-37 (Pubitemid 40125471)
68. Moreno S, Farioli-Vecchioli S, Ceru MP. Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 2004;123:131-45 (Pubitemid 37518482)
69. Churi SB, Abdel-Aleem OS, Tumber KK, et al. Intrathecal rosiglitazone acts at peroxisome proliferator-activated receptor-gamma to rapidly inhibit neuropathic pain in rats. J Pain 2008;9:639-49
70. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem 2000;43:527-50 (Pubitemid 30127149)
71. Bernardo A, Ajmone-Cat MA, Levi G, Minghetti L. 15-deoxy- Delta12,14-prostaglandin J2 regulates the functional state and the survival of microglial cells through multiple molecular mechanisms. J Neurochem 2003;87:742-51 (Pubitemid 37310639)
72. Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med 2004;10:355-61 (Pubitemid 38508511)
73. Ziouzenkova O, Perrey S, Asatryan L, et al. Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: evidence for an antiinflammatory role for lipoprotein lipase. Proc Natl Acad Sci USA 2003;100:2730-5 (Pubitemid 36297567)
74. Fitzpatrick FA, Wynalda MA. Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro. J Biol Chem 1983;258:11713-18 (Pubitemid 13019315)
75. Forman BM, Tontonoz P, Chen J, et al. 15-Deoxy-Delta12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 1995;83:803-12 (Pubitemid 3006324)
76. Scher JU, Pillinger MH. 15d-PGJ2: the anti-inflammatory prostaglandin? Clin Immunol 2005;114:100-9
77. Wolf G. Adipocyte differentiation is regulated by a prostaglandin liganded to the nuclear peroxisome proliferator-activated receptor. Nutr Rev 1996;54:290-2 (Pubitemid 27075900)
78. Genovese T, Cuzzocrea S, Di Paola R, et al. Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury. Eur Respir J 2005;25:225-34 (Pubitemid 40246521)
79. Boyault S, Bianchi A, Moulin D, et al. 15-Deoxy-Delta12,14-prostaglandin J2 inhibits IL-1beta-induced IKK enzymatic activity and IkappaBalpha degradation in rat chondrocytes through a PPARgamma-independent pathway. FEBS Lett 2004;572:33-40 (Pubitemid 39092509)
80. Cheatham WW. Peroxisome proliferator-activated receptor translational research and clinical experience. Am J Clin Nutr 2010;91:262S-6S
81. Knouff C, Auwerx J. Peroxisome proliferator-activated receptor-gamma calls for activation in moderation: lessons from genetics and pharmacology. Endocr Rev 2004;25:899-918 (Pubitemid 39657772)
82. Agarwal AK, Garg A. Genetic basis of lipodystrophies and management of metabolic complications. Annu Rev Med 2006;57:297-311 (Pubitemid 43261993)
83. Simo R, Rodriguez A, Caveda E. Different effects of thiazolidinediones on cardiovascular risk in patients with type 2 diabetes mellitus: pioglitazone versus rosiglitazone. Curr Drug Saf 2010;5:234-44
84. Krishnaswami A, Ravi-Kumar S, Lewis JM. Thiazolidinediones: a 2010 perspective. Perm J 2010;14:64-72
85. Shah A, Rader DJ, Millar JS. The effect of PPAR-alpha agonism on apolipoprotein metabolism in humans. Atherosclerosis 2010;210:35-40
86. Leibowitz MD, Fievet C, Hennuyer N, et al. Activation of PPARDelta alters lipid metabolism in db/db mice. FEBS Lett 2000;473:333-6 (Pubitemid 30249149)
87. Hall JM, McDonnell DP. The molecular mechanisms underlying the proinflammatory actions of thiazolidinediones in human macrophages. Mol Endocrinol 2007;21:1756-68 (Pubitemid 47173789)
88. Gonzalez FJ. Recent update on the PPARalpha-null mouse. Biochimie 1997;79:139-44
89. Cunard R, Ricote M, DiCampli D, et al. Regulation of cytokine expression by ligands of peroxisome proliferator activated receptors. J Immunol 2002;168:2795-802 (Pubitemid 34211658)
90. Delerive P, De Bosscher K, Besnard S, et al. Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 1999;274:32048-54
91. Kockx M, Gervois PP, Poulain P, et al. Fibrates suppress fibrinogen gene expression in rodents via activation of the peroxisome proliferator-activated receptor-alpha. Blood 1999;93:2991-8 (Pubitemid 29200791)
92. Madej A, Okopien B, Kowalski J, et al. Effects of fenofibrate on plasma cytokine concentrations in patients with atherosclerosis and hyperlipoproteinemia IIb. Int J Clin Pharmacol Ther 1998;36:345-9 (Pubitemid 28271555)
93. Lovett-Racke AE, Hussain RZ, Northrop S, et al. Peroxisome proliferator-activated receptor alpha agonists as therapy for autoimmune disease. J Immunol 2004;172:5790-8 (Pubitemid 38542085)
94. Cunard R, DiCampli D, Archer DC, et al. WY14,643, a PPARalpha ligand, has profound effects on immune responses in vivo. J Immunol 2002;169:6806-12 (Pubitemid 36899265)
95. Poynter ME, Daynes RA. Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging. J Biol Chem 1998;273:32833-41 (Pubitemid 28557672)
96. Gocke AR, Hussain RZ, Yang Y, et al. Transcriptional modulation of the immune response by peroxisome proliferator-activated receptor-alpha agonists in autoimmune disease. J Immunol 2009;182:4479-87
97. Li AC, Binder CJ, Gutierrez A, et al. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/Delta, and gamma. J Clin Invest 2004;114:1564-76 (Pubitemid 40385547)
98. Berry A, Balard P, Coste A, et al. IL-13 induces expression of CD36 in human monocytes through PPARgamma activation. Eur J Immunol 2007;37:1642-52 (Pubitemid 46939499)
99. Kostadinova R, Wahli W, Michalik L. PPARs in diseases: control mechanisms of inflammation. Curr Med Chem 2005;12:2995-3009 (Pubitemid 41672488)
100. Alarcon de la Lastra C, Sanchez-Fidalgo S, Villegas I, Motilva V. New pharmacological perspectives and therapeutic potential of PPAR-gamma agonists. Curr Pharm Des 2004;10:3505-24 (Pubitemid 39378330)
101. Shie FS, Nivison M, Hsu PC, et al. Modulation of microglial innate immunity in Alzheimer's disease by activation of peroxisome proliferator- activated receptor gamma. Curr Med Chem 2009;16:643-51
102. Sundararajan S, Jiang Q, Heneka M, Landreth G. PPARgamma as a therapeutic target in central nervous system diseases. Neurochem Int 2006;49:136-44 (Pubitemid 43867071)
103. Haffner SM, Greenberg AS, Weston WM, et al. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 2002;106:679-84 (Pubitemid 34851926)
104. Setoguchi K, Misaki Y, Terauchi Y, et al. Peroxisome proliferator- activated receptor-gamma haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis. J Clin Invest 2001;108:1667-75 (Pubitemid 33144877)
105. Barish GD, Downes M, Alaynick WA, et al. A Nuclear Receptor Atlas: macrophage activation. Mol Endocrinol 2005;19:2466-77 (Pubitemid 41362661)
106. Marx N, Schonbeck U, Lazar MA, et al. Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 1998;83:1097-103 (Pubitemid 28533518)
107. Murao K, Imachi H, Momoi A, et al. Thiazolidinedione inhibits the production of monocyte chemoattractant protein-1 in cytokine-treated human vascular endothelial cells. FEBS Lett 1999;454:27-30 (Pubitemid 29296919)
108. Clark RB, Bishop-Bailey D, Estrada-Hernandez T, et al. The nuclear receptor PPARgamma and immunoregulation: PPARgamma mediates inhibition of helper T cell responses. J Immunol 2000;164:1364-71 (Pubitemid 30067250)
109. Zapata-Gonzalez F, Rueda F, Petriz J, et al. Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPARgamma:RXR heterodimers: comparison with other polyunsaturated fatty acids. J Leukoc Biol 2008;84:1172-82
110. Straus DS, Pascual G, Li M, et al. 15-deoxy-Delta12,14-prostaglandin J2 inhibits multiple steps in the NF-kappaB signaling pathway. Proc Natl Acad Sci USA 2000;97:4844-9 (Pubitemid 30238645)
111. Chawla A, Barak Y, Nagy L, et al. PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med 2001;7:48-52 (Pubitemid 32095641)
112. Welch JS, Ricote M, Akiyama TE, et al. PPARgamma and PPARDelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages. Proc Natl Acad Sci USA 2003;100:6712-17 (Pubitemid 36666645)
113. Dunn SE, Bhat R, Straus DS, et al. Peroxisome proliferator-activated receptor delta limits the expansion of pathogenic Th cells during central nervous system autoimmunity. J Exp Med 2010;207:1599-608
114. Desvergne B. PPARDelta/beta: the lobbyist switching macrophage allegiance in favor of metabolism. Cell Metab 2008;7:467-9 (Pubitemid 351729210)
115. Barish GD, Atkins AR, Downes M, et al. PPARDelta regulates multiple proinflammatory pathways to suppress atherosclerosis. Proc Natl Acad Sci USA 2008;105:4271-6 (Pubitemid 351754370)
116. Ding G, Cheng L, Qin Q, et al. PPARDelta modulates lipopolysaccharide- induced TNFalpha inflammation signaling in cultured cardiomyocytes. J Mol Cell Cardiol 2006;40:821-8 (Pubitemid 43817042)
117. Kharroubi I, Lee CH, Hekerman P, et al. BCL-6: a possible missing link for anti-inflammatory PPAR-Delta signalling in pancreatic beta cells. Diabetologia 2006;49:2350-8 (Pubitemid 44359096)
118. Bouhlel MA, Brozek J, Derudas B, et al. Unlike PPARgamma, PPARalpha or PPARbeta/Delta activation does not promote human monocyte differentiation toward alternative macrophages. Biochem Biophys Res Commun 2009;386:459-62
119. Kang K, Reilly SM, Karabacak V, et al. Adipocyte-derived Th2 cytokines and myeloid PPARDelta regulate macrophage polarization and insulin sensitivity. Cell Metab 2008;7:485-95 (Pubitemid 351729204)
120. Xu J, Storer PD, Chavis JA, et al. Agonists for the peroxisome proliferator-activated receptor-alpha and the retinoid X receptor inhibit inflammatory responses of microglia. J Neurosci Res 2005;81:403-11 (Pubitemid 41359295)
121. Bernardo A, Levi G, Minghetti L. Role of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its natural ligand 15-deoxy-Delta12,14-prostaglandin J2 in the regulation of microglial functions. Eur J Neurosci 2000;12:2215-23 (Pubitemid 30497019)
122. Szeles L, Torocsik D, Nagy L. PPARgamma in immunity and inflammation: cell types and diseases. Biochim Biophys Acta 2007;1771:1014-30 (Pubitemid 47202035)
123. Luconi M, Cantini G, Serio M. Peroxisome proliferator-activated receptor gamma (PPARgamma): is the genomic activity the only answer? Steroids 2010;75:585-94
124. Malaspina A, Turkheimer F. A review of the functional role and of the expression profile of retinoid signaling and of nuclear receptors in human spinal cord. Brain Res Bull 2007;71:437-46 (Pubitemid 46157165)
125. Malaspina A, Michael-Titus AT. Is the modulation of retinoid and retinoid-associated signaling a future therapeutic strategy in neurological trauma and neurodegeneration? J Neurochem 2008;104:584-95
126. Bregman BS, Diener PS, McAtee M, et al. Intervention strategies to enhance anatomical plasticity and recovery of function after spinal cord injury. Adv Neurol 1997;72:257-75
127. Yi JH, Park SW, Brooks N, et al. PPARgamma agonist rosiglitazone is neuroprotective after traumatic brain injury via anti-inflammatory and anti-oxidative mechanisms. Brain Res 2008;1244:164-72
128. Genovese T, Esposito E, Mazzon E, et al. Effect of cyclopentanone prostaglandin 15-deoxy- Delta12,14PGJ2 on early functional recovery from experimental spinal cord injury. Shock 2008;30:142-52
129. McTigue DM, Tripathi R, Wei P, Lash AT. The PPAR gamma agonist Pioglitazone improves anatomical and locomotor recovery after rodent spinal cord injury. Exp Neurol 2007;205:396-406 (Pubitemid 46755761)
130. Park SW, Yi JH, Miranpuri G, et al. Thiazolidinedione class of peroxisome proliferator-activated receptor gamma agonists prevents neuronal damage, motor dysfunction, myelin loss, neuropathic pain, and inflammation after spinal cord injury in adult rats. J Pharmacol Exp Ther 2007;320:1002-12 (Pubitemid 46294061)
131. Zhang Q, Hu W, Meng B, Tang T. PPARgamma agonist rosiglitazone is neuroprotective after traumatic spinal cord injury via anti-inflammatory in adult rats. Neurol Res 2010;32:852-9
132. Churi SB, Abdel-Aleem OS, Tumber KK, et al. Intrathecal rosiglitazone acts at peroxisome proliferator-activated receptor-gamma to rapidly inhibit neuropathic pain in rats. J Pain 2008;9:639-49
133. Maeda T, Kiguchi N, Kobayashi Y, et al. Pioglitazone attenuates tactile allodynia and thermal hyperalgesia in mice subjected to peripheral nerve injury. J Pharmacol Sci 2008;108:341-7
134. Morgenweck J, Abdel-Aleem OS, McNamara KC, et al. Activation of peroxisome proliferator-activated receptor gamma in brain inhibits inflammatory pain, dorsal horn expression of Fos, and local edema. Neuropharmacology 2010;58:337-45
135. McTigue DM. Potential therapeutic targets for PPARgamma after spinal cord injury. PPAR Res 2008;2008:517162
136. van Neerven S, Mey J. RAR/RXR and PPAR/RXR signaling in spinal cord injury. PPAR Res 2007;2007:29275
137. Cuzzocrea S, Di Paola R, Mazzon E, et al. Role of endogenous and exogenous ligands for the peroxisome proliferators activated receptors alpha (PPAR-alpha) in the development of inflammatory bowel disease in mice. Lab Invest 2004;84:1643-54 (Pubitemid 39600571)
138. Gouni-Berthold I, Krone W. Peroxisome proliferator-activated receptor alpha (PPAR-alpha) and athero-sclerosis. Curr Drug Targets Cardiovasc Haematol Disord 2005;5:513-23
139. Colville-Nash P, Willis D, Papworth J, et al. The peroxisome proliferator-activated receptor alpha activator, Wy14,643, is anti-inflammatory in vivo. Inflammopharmacology 2005;12:493-504 (Pubitemid 41607353)
140. Genovese T, Mazzon E, Di Paola R, et al. Role of endogenous ligands for the peroxisome proliferators activated receptors alpha in the secondary damage in experimental spinal cord trauma. Exp Neurol 2005;194:267-78 (Pubitemid 40719761)
141. Genovese T, Esposito E, Mazzon E, et al. PPAR-alpha modulate the anti-inflammatory effect of glucocorticoids in the secondary damage in experimental spinal cord trauma. Pharmacol Res 2009;59:338-50
142. Lo Verme J, Fu J, Astarita G, et al. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol 2005;67:15-19 (Pubitemid 40069962)
143. Genovese T, Esposito E, Mazzon E, et al. Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury. J Pharmacol Exp Ther 2008;326:12-23 (Pubitemid 351872139)
144. Almad A, McTigue DM. Chronic expression of PPAR-Delta by oligodendrocyte lineage cells in the injured rat spinal cord. J Comp Neurol 2010;518:785-99
145. Paterniti I, Esposito E, Mazzon E, et al. Evidence for the role of peroxisome proliferator-activated receptor-beta/Delta in the development of spinal cord injury. J Pharmacol Exp Ther 2010;333:465-77
146. Iwashita A, Muramatsu Y, Yamazaki T, et al. Neuroprotective efficacy of the peroxisome proliferator-activated receptor Delta-selective agonists in vitro and in vivo. J Pharmacol Exp Ther 2007;320:1087-96 (Pubitemid 46294065)
147. Chan CC. Inflammation: beneficial or detrimental after spinal cord injury? Recent Pat CNS Drug Discov 2008;3:189-99
148. Esposito E, Cuzzocrea S. Anti-TNF therapy in the injured spinal cord. Trends Pharmacol Sci 2011;32:107-15
149. Renault-Mihara F, Okada S, Shibata S, et al. Spinal cord injury: emerging
150. Sauerbeck A, Gao J, Readnower R, et al. Pioglitazone attenuates mitochondrial dysfunction, cognitive impairment, cortical tissue loss, and inflammation following traumatic brain injury. Exp Neurol 2011;227:128-35