Nuclear receptors in macrophage biology: At the crossroads of lipid metabolism and inflammation

Annual Review of Cell and Developmental Biology

Volumn 20, Issue , 2004, Pages 455-480

  Castrillo, Antonio ^a   Tontonoz, Peter ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Atherosclerosis; Liver X receptors; Oxidized lipids; Peroxisome proliferator activated receptors

Indexed keywords

CELL NUCLEUS RECEPTOR; LIVER X RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA;

ATHEROSCLEROSIS; BACTERIAL INFECTION; CARDIOVASCULAR RISK; CHOLESTEROL METABOLISM; CHOLESTEROL TRANSPORT; FATTY ACID METABOLISM; GENE EXPRESSION; HUMAN; IMMUNOMODULATION; INFLAMMATION; LIPID TRANSPORT; MACROPHAGE ACTIVATION; MACROPHAGE FUNCTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; TOOTH INFECTION; TRANSCRIPTION REGULATION; VIRUS INFECTION;

ANIMALS; HUMANS; INFLAMMATION; LIPID METABOLISM; MACROPHAGES; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; RECEPTORS, CYTOPLASMIC AND NUCLEAR;

BACTERIA (MICROORGANISMS);

EID: 8444233254     PISSN: 10810706     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.cellbio.20.012103.134432     Document Type: Review

References (118)

1. Aiello RJ, Brees D, Bourassa PA, Royer L, Lindsey S, et al. 2002. Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages. Arterioscler. Thromb. Vasc. Biol. 22:630-37
2. Akiyama TE, Sakai S, Lambert G, Nicol CJ, Matsusue K, et al. 2002. Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol. Cell Biol. 22:2607-19
3. Alberti S, Schuster G, Parini P, Feltkamp D, Diczfalusy U, et al. 2001. Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta-deficient mice. J. Clin. Invest. 107:565-73
4. Apfel R, Benbrook D, Lernhardt E, Ortiz MA, Salbert G, et al. 1994. A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. Mol. Cell Biol. 14:7025-35
5. Barak Y, Liao D, He W, Ong ES, Nelson MC, et al. 2002. Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer. Proc. Natl. Acad. Sci. USA 99:303-8
6. Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, et al. 1999. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol. Cell 4:585-95
7. Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, et al. 1999. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402:880-83
8. Berthou L, Duverger N, Emmanuel F, Langouet S, Auwerx J, et al. 1996. Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice. J. Clin. Invest. 97:2408-16
9. Bodzioch M, Orso E, Klucken J, Langmann T, Bottcher A, et al. 1999. The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat. Genet. 22:347-51
10. Bright JJ, Natarajan C, Muthian G, Barak Y, Evans RM. 2003. Peroxisome proliferator-activated receptor-gamma-deficient heterozygous mice develop an exacerbated neural antigen-induced Th1 response and experimental allergic encephalomyelitis. J. Immunol. 171:5743-50
11. Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, et al. 1999. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat. Genet. 22:336-45
12. Byrne GI, Kalayoglu MV. 1999. Chlamydia pneumoniae and atherosclerosis: links to the disease process. Am. Heart J. 138:S488-90
13. Cao G, Beyer TP, Yang XP, Schmidt RJ, Zhang Y, et al. 2002. Phospholipid transfer protein is regulated by liver X receptors in vivo. J. Biol. Chem. 277:39561-65
14. Cao G, Liang Y, Broderick CL, Oldham BA, Beyer TP, et al. 2003. Antidiabetic action of a liver X receptor agonist mediated by inhibition of hepatic gluconeogenesis. J. Biol. Chem. 278:1131-36
15. Castrillo A, Diaz-Guerra MJ, Hortelano S, Martin-Sanz P, Bosca L. 2000. Inhibition of IkappaB kinase and IkappaB phosphorylation by 15-deoxy-Delta(12, 14)-prostaglandin J(2) in activated murine macrophages. Mol. Cell Biol. 20:1692-98
16. Castrillo A, Joseph SB, Marathe C, Mangelsdorf DJ, Tontonoz P. 2003a. Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages. J. Biol. Chem. 278:10443-49
17. Castrillo A, Joseph SB, Vaidya SA, Haberland M, Fogelman AM, et al. 2003b. Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol. Cell 12:805-16
18. Chawla A, Barak Y, Nagy L, Liao D, Tontonoz P, et al. 2001a. PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat. Med. 7:48-52
19. Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, et al. 2001b. A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol. Cell 7:161-71
20. Chawla A, Lee CH, Barak Y, He W, Rosenfeld J, et al. 2003. PPARdelta is a very low-density lipoprotein sensor in macrophages. Proc. Natl. Acad. Sci. USA 100:1268-73
21. Chinetti G, Gbaguidi FG, Griglio S, Mallat Z, Antonucci M, et al. 2000. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 101:2411-17
22. Chinetti G, Griglio S, Antonucci M, Torra IP, Delerive P, et al. 1998. Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. J. Biol. Chem. 273:25573-80
23. Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, et al. 2001. PRAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat. Med. 7:53-58
24. Chiu B, Viira E, Tucker W, Fong IW. 1997. Chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery. Circulation 96:2144-48
25. Costet P, Luo Y, Wang N, Tall AR. 2000. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J. Biol. Chem. 275:28240-45
26. Curtiss LK. 2000. ApoE in atherosclerosis: a protein with multiple hats. Arterioscler. Thromb. Vasc. Biol. 20:1852-53
27. Dalen KT, Ulven SM, Bamberg K, Gustafsson JA, Nebb HI. 2003. Expression of the insulin-responsive glucose transporter GLUT4 in adipocytes is dependent on liver X receptor alpha. J. Biol Chem. 278:48283-91
28. Desreumaux P, Dubuquoy L, Nutten S, Peuchmaur M, Englaro W, et al. 2001. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer. A basis for new therapeutic strategies. J. Exp. Med. 193:827-38
29. Desrumaux CM, Mak PA, Boisvert WA, Masson D, Stupack D, et al. 2003. Phospholipid transfer protein is present in human atherosclerotic lesions and is expressed by macrophages and foam cells. J. Lipid Res. 44:1453-61
30. Dreyer C, Keller H, Mahfoudi A, Laudet V, Krey G, et al. 1993. Positive regulation of the peroxisomal beta-oxidation pathway by fatty acids through activation of peroxisome proliferator-activated receptors (PPAR). Biol. Cell 77:67-76
31. Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, et al. 1992. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68:879-87
32. Duez H, Chao YS, Hernandez M, Torpier G, Poulain P et al. 2002. Reduction of atherosclerosis by the peroxisome proliferator-activated receptor alpha agonist fenofibrate in mice. J. Biol. Chem. 277:48051-57
33. Fernandez-Real JM, Ricart W. 2003. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr. Rev. 24:278-301
34. Finck BN, Han X, Courtois M, Aimond F, Nerbonne JM, et al. 2003. A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. Proc. Natl. Acad. Sci. USA 100:1226-31
35. Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, et al. 2002. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J. Clin. Invest. 109:121-30
36. Forman BM, Chen J, Evans RM. 1997. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc. Natl. Acad. Sci. USA 94:4312-17
37. Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, et al. 1995. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83:803-12
38. Fowler AJ, Sheu MY, Schmuth M, Kao J, Fluhr JW, et al. 2003. Liver X receptor activators display anti-inflammatory activity in irritant and allergic contact dermatitis models: liver-X-receptor-specific inhibition of inflammation and primary cytokine production. J. Invest. Dermatol. 120:246-55
39. Francis GA, Annicotte JS, Auwerx J. 2003a. PPAR agonists in the treatment of atherosclerosis. Curr. Opin. Pharmacol. 3:186-91
40. Francis GA, Fayard E, Picard F, Auwerx J. 2003b. Nuclear receptors and the control of metabolism. Annu. Rev. Physiol. 65:261-311
41. Glass CK, Rosenfeld MG. 2000. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 14:121-41
42. Glass CK, Witztum JL. 2001. Atherosclerosis. The road ahead. Cell 104:503-16
43. Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, et al. 2002. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 106:679-84
44. Huang JT, Welch JS, Ricote M, Binder CJ, Willson TM, et al. 1999. Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature 400:378-82
45. Issemann I, Green S. 1990. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347:645-50
46. Janeway CA Jr., Medzhitov R. 2002. Innate immune recognition. Annu. Rev. Immunol. 20:197-216
47. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. 1996. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383:728-31
48. Jiang C, Ting AT, Seed B. 1998. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82-86
49. Joseph SB, Castrillo A, Laffitte BA, Mangelsdorf DJ, Tontonoz P. 2003. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat. Med. 9:213-19
50. Joseph SB, McKilligin E, Pei L, Watson MA, Collins AR, et al. 2002. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc. Natl. Acad. Sci. USA 99:7604-9
51. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, et al. 1999. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J. Clin. Invest. 103:1489-98
52. Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, et al. 1994. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. USA 91:7355-59
53. Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, et al. 1995. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 83:813-19
54. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, et al. 1997. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc. Natl. Acad. Sci. USA 94:4318-23
55. Kubota N, Terauchi Y, Miki H, Tamemoto H, Yamauchi T, et al. 1999. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol. Cell 4:597-609
56. Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S, et al. 2003a. Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc. Natl. Acad. Sci. USA 100:5419-24
57. Laffitte BA, Joseph SB, Chen M, Castrillo A, Repa J, et al. 2003b. The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions. Mol. Cell Biol. 23:2182-91
58. Laffitte BA, Joseph SB, Walczak R, Pei L, Wilpitz DC, et al. 2001a. Autoregulation of the human liver X receptor alpha promoter. Mol. Cell Biol. 21:7558-68
59. Laffitte BA, Repa JJ, Joseph SB, Wilpitz DC, Kast HR, et al. 2001b. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc. Natl. Acad. Sci. USA 98:507-12
60. Lee CH, Chawla A, Urbiztondo N, Liao D, Boisvert WA, et al. 2003. Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science 302:453-57
61. Lee MH, Lu K, Patel SB. 2001. Genetic basis of sitosterolemia. Curr. Opin. Lipidol. 12:141-49
62. Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, et al. 1997. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J. Biol. Chem. 272:3137-40
63. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, et al. 1995. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J. Biol. Chem. 270:12953-56
64. Leibowitz MD, Fievet C, Hennuyer N, Peinado-Onsurbe J, Duez H, et al. 2000. Activation of PPARdelta alters lipid metabolism in db/db mice. FEBS Lett. 473:333-36
65. Leone TC, Weinheimer CJ, Kelly DP. 1999. A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc. Natl. Acad. Sci. USA 96:7473-78
66. Li AC, Brown KK, Silvestre MJ, Willson TM, Palinski W, et al. 2000. Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J. Clin. Invest. 106:523-31
67. Mak PA, Kast-Woelbern HR, Anisfeld AM, Edwards PA. 2002a. Identification of PLTP as an LXR target gene and apoE as an FXR target gene reveals overlapping targets for the two nuclear receptors. J. Lipid Res. 43:2037-41
68. Mak PA, Laffitte BA, Desrumaux C, Joseph SB, Curtiss LK, et al. 2002b. Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta. J. Biol. Chem. 277:31900-8
69. Mangelsdorf DJ, Evans RM. 1995. The RXR heterodimers and orphan receptors. Cell 83:841-50
70. Marx N, Sukhova G, Murphy C, Libby P, Plutzky J. 1998. 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. 153:17-23
71. Marx N, Sukhova GK, Collins T, Libby P, Plutzky J. 1999. PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 99:3125-31
72. Moore KJ, Rosen ED, Fitzgerald ML, Randow F, Andersson LP, et al. 2001. The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Nat. Med. 7:41-47
73. Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM. 1998. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 93:229-40
74. Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, et al. 1998. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature 395:137-43
75. Oliver WR Jr., Shenk JL, Snaith MR, Russell CS, Plunket KD, et al. 2001. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc. Natl. Acad. Sci. USA 98:5306-11
76. Peet DJ, Janowski BA, Mangelsdorf DJ. 1998a. The LXRs: a new class of oxysterol receptors. Curr. Opin. Genet Dev. 8:571-75
77. Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, et al. 1998b. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 93:693-704
78. Peters JM, Lee SS, Li W, Ward JM, Gavrilova O, et al. 2000. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol. Cell Biol. 20:5119-28
79. Plutzky J. 2003. The potential role of peroxisome proliferator-activated receptors on inflammation in type 2 diabetes mellitus and atherosclerosis. Am. J. Cardiol. 92:34J-41J
80. Rassu M, Cazzavillan S, Scagnelli M, Peron A, Bevilacqua PA, et al. 2001. Demonstration of Chlamydia pneumoniae in atherosclerotic arteries from various vascular regions. Atherosclerosis 158:73-79
81. Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, et al. 2002. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J. Biol. Chem. 277:18793-800
82. Repa JJ, Mangelsdorf DJ. 2000. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu. Rev. Cell Dev. Biol. 16:459-81
83. Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, et al. 2000. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289:1524-29
84. Ricote M, Huang J, Fajas L, Li A, Welch J, et al. 1998a. Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc. Natl. Acad. Sci. USA 95:7614-19
85. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. 1998b. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391:79-82
86. Robinson-Rechavi M, Escriva Garcia H, Laudet V. 2003. The nuclear receptor superfamily. J. Cell Sci. 116:585-86
87. Rosen ED, Spiegelman BM. 2000. Molecular regulation of adipogenesis. Annu. Rev. Cell Dev. Biol. 16:145-71
88. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, et al. 1999. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N. Engl. J. Med. 341:410-18
89. Rust S, Rosier M, Funke H, Real J, Amoura Z, et al. 1999. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat. Genet. 22:352-55
90. Schmitz G, Langmann T, Heimerl S. 2001. Role of ABCG1 and other ABCG family members in lipid metabolism. J. Lipid Res. 42:1513-20
91. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, et al. 1996. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 15:5336-48
92. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, et al. 2000. Role of LXRs in control of lipogenesis. Genes Dev. 14:2831-38
93. Schuster GU, Parini P, Wang L, Alberti S, Steffensen KR, et al. 2002. Accumulation of foam cells in liver X receptor-deficient mice. Circulation 106:1147-53
94. Schwartz K, Lawn RM, Wade DP. 2000. ABC1 gene expression and ApoA-I-mediated cholesterol efflux are regulated by LXR. Biochem. Biophys. Res. Commun. 274:794-802
95. Setoguchi K, Misaki Y, Terauchi Y, Yamauchi T, Kawahata K, et al. 2001. Peroxisome proliferator-activated receptor-gamma haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis. J. Clin. Invest. 108:1667-75
96. Spiegel man BM, Flier JS. 2001. Obesity and the regulation of energy balance. Cell 104:531-43
97. Staels B, Koenig W, Habib A, Merval R, Lebret M, et al. 1998. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 393:790-93
98. Straus DS, Pascual G, Li M, Welch JS, Ricote M, et al. 2000. 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway. Proc. Natl. Acad. Sci. USA 97:4844-49
99. Su CG, Wen X, Bailey ST, Jiang W, Rangwala SM, et al. 1999. A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J. Clin. Invest. 104:383-89
100. Tan NS, Michalik L, Noy N, Yasmin R, Pacot C, et al. 2001. Critical roles of PPAR beta/delta in keratinocyte response to inflammation. Genes Dev. 15:3263-77
101. Tangirala RK, Bischoff ED, Joseph SB, Wagner BL, Walczak R, et al. 2002. Identification of macrophage liver X receptors as inhibitors of atherosclerosis. Proc. Natl. Acad. Sci. USA 99:11896-901
102. Tontonoz P, Hu E, Spiegelman BM. 1994. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79:1147-56
103. Tontonoz P, Mangelsdorf DJ. 2003. Liver X receptor signaling pathways in cardiovascular disease. Mol. Endocrinol. 17:985-93
104. Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM. 1998. PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93:241-52
105. Tordjman K, Bernal-Mizrachi C, Zemany L, Weng S, Feng C, et al. 2001. PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice. J. Clin. Invest. 107:1025-34
106. van Eck M, Bos IS, Kaminski WE, Orso E, Rothe G, et al. 2002. Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc. Natl. Acad. Sci. USA 99:6298-303
107. Venkateswaran A, Laffitte BA, Joseph SB, Mak PA, Wilpitz DC, et al. 2000a. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc. Natl. Acad. Sci. USA 97:12097-102
108. Venkateswaran A, Repa JJ, Lobaccaro JM, Bronson A, Mangelsdorf DJ, et al. 2000b. Human white/murine ABC8 mRNA levels are highly induced in lipid-loaded macrophages. A transcriptional role for specific oxysterols. J. Biol. Chem. 275:14700-7
109. Vosper H, Patel L, Graham TL, Khoudoli GA, Hill A, et al. 2001. The peroxisome proliferator-activated receptor delta promotes lipid accumulation in human macrophages. J. Biol. Chem. 276:44258-65
110. Vu-Dac N, Schoonjans K, Kosykh V, Dallongeville J, Fruchart JC, et al. 1995. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J. Clin. Invest. 96:741-50
111. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, et al. 2003. Peroxisome- proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 113:159-70
112. Welch JS, Ricote M, Akiyama TE, Gonzalez FJ, Glass CK. 2003. PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages. Proc. Natl. Acad. Sci. USA 100:6712-17
113. Whitney KD, Watson MA, Goodwin B, Galardi CM, Maglich JM, et al. 2001. Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages. J. Biol. Chem. 276:43509-15
114. Willson TM, Jones SA, Moore JT, Kliewer SA. 2001a. Chemical genomics: functional analysis of orphan nuclear receptors in the regulation of bile acid metabolism. Med. Res. Rev. 21:513-22
115. Willson TM, Lambert MH, Kliewer SA. 2001b. Peroxisome proliferator-activated receptor gamma and metabolic disease. Annu. Rev. Biochem. 70:341-67
116. Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, et al. 1995. LXR, a nuclear receptor that defines adistinct retinoid response pathway. Genes Dev. 9:1033-45
117. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, et al. 1999. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol. Cell 3:397-403
118. Ziouzenkova O, Perrey S, Asatryan L, Hwang J, MacNaul KL, et al. 2003. Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: evidence for an antiinflammatory role for lipoprotein lipase. Proc. Natl. Acad. Sci. USA 100:2730-35