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@ ↓COX・2含

Ligands ← ABCAl

lCP・1

査P臥Rα

Macrophage PPARγ

図11:マクロファージにおける、酸化LDLによるPPARs活性化機序の模式図

マクロファージに酸化LDLが作用すると、酸化LDL中の9-HODE、13-HODE、酸化リン脂質がPPARの

直接的なリガンドとなりPPARα、 PPARγを活性化する。一方で、酸化LDLはERKI/2を介した、 COX-2 の過剰発現を誘導し、COX-2の過剰発現が細胞内15d-PGJ2を増加させ、 PPARα、 PPARγの活性化を誘導 する。PPARα、 PPARγの活性化はABCAIのmRNA発現を増加し、 MCP-1のmRNA発現を抑制する。

AA : arachidonic acict ABCAI : ArlP-bindmg cassette transporter Al, COX-2 : cycloxygenase-2,

15d-PGJ2 : 15-deoxy-A’2’i4-prostaglandm J2, ERKI/2 : extracellular・一signal regulated kinase 1/2,

HODE : hydroxyoctadecadienoic acid, Ox-LDL : oxidized low-density lipoprotein,

PPAR : peroxisome proliferator-activated receptor

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10.参考文献

Bendriss-Vermare N, Barthelemy C, Durand 1, Bruand C, Dezutter-Dambuyant C, Moulian N,

Berrih-Aknin S, Caux C, Trinchieri G Briere E 2001; Human thymus contains

IFN-alpha-producing CD l l c(一), myeloid CD l l c(+), and mature interdigitating dendritic cells. J CIin lnvest. 107:835-844.

Burleigh ME, Babaev VR, Oates JA, Harris RC, Gautam S, Riendeau D, Marnett LJ,

Morrow JD, Fazio S, Linton ME 2002; Cyclooxygenase-2 promotes early atherosclerotic lesion formation in LDL receptor-deficient mice. Circulation. 105:1816-1823.

Campbell WB, Halushka PV. 1996; Lipid-derived autacoids: eicosanoids and platelet-activating factor. ln: The Pharmacological Basis ofTherapeutics. Hardman JG and Limbird LE (eds). 9th edition. McGraw-Hill. New York :601一一616.

       ,

Charo凪Taubman MB.2004;Chemokines in the pathogenesis of vascular disease. Circ Res.

95:858-866.

Chinetti G Lestavel S, Bocher V, Remaley AT, Neve B, Torra ll}, Teissier E, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V, Staels B. 20el; PPARor and PPARy activators induce cholesterol removal from human macrophage foam cells through stimulation of the AB CA1 pathway. Nat Med. 7:53-58.

Chodakewitz JA, Kupper TS, Coleman DL 1988; Keratinocyte-derived

granulocyte/macrophage colony-stimulating factor induces DNA synthesis by peritoneal macrophages. J Immunol. 140:832-836.

Claus R, Fyrnys B, Deigner H ?, Wolf G. 1996; Oxidized low-density lipoprotein stimulates protein kinase C (PKC) and induces expression of PKC・・lsotypes via prostaglandin-H-synthase in P388D 1 macrophage-like cells. Biochemistr y. 35:491 1-4922.

Delerivea P, Furmana C, Teissiera E, Frucharta JC, Durieza P, Staels B. 2000; Oxidized phospholipids activate PPARodn a phospholipase A2-dependent manner. FEBS lett. 471:34-38.

58

FitzGerald GA. 2004; Coxib s and cardiovascular disease. N Engl JMed. 351:1709-171 1.

Folch J, Lees M, Sloane S伽1ey GH:.1957;A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 226:497-509.

Forman BM, Chen J, Evans RM. 1997; Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors ct and 6. Proc Natl Acad Sci USA. 94:4312-4317.

Fuj iwara Y, Kiyota N, Hori M, Matsushita S, lij ima Y, Aoki K, Shibata D, Takeya M,

Ikeda T, Nohara T, Nagai R. 2007: Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT. Arterioscler 7hromb Vasc BioL 27:2400-2406.

Furberg CD, Psaty BM, FitzGerald GA. 20e5; Parecoxib, valdecoxib, and cardiovascular risk.

Circulation. 111:249.

Goldstein JL, Ho YK, Basu SK and Brown MS. 1979; Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci USA. 76:333-337.

Hu J, Roy SK, S血叩iro PS, Rodig SR, Reddy SP, Platanias LC, Schreiber RD, Kalvakolanu DV. 2001; ERK I and ERK2 activate CCAAATIenhancer-binding protein-B-dependent gene transcription in response to interferon-y. J Biol Chem. 276:287-297.

Hakamata H, Miyazaki A, Sakai M, Suginohara Y;Sak鋤moto Y;Ho血chi S.1994;Species

diffbrence in cholesteryl ester cycle and HDL-induced cholesterol e田ux丘om macrophage fbam cells. Arterioscler Zhromb Vasc Biol. 14:1860-1865.

Hamilton TA, Maj or JA, Chisolm GM. 1995; The effects of oxidized low density lipoproteins on inducible mouse macrophage gene expression are gene and stimulus dependent. 」 Cli.n lnvest.

95:2020-2027.

Henriksen T, Mahoney EM, Steinberg D. 1981; Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors

       59

for acetylated low density lipoproteins. Proc Natl Acad Sci USA. 78:6499-6503.

Hernindez-Presa MA, Manin-Ventura JL, Ortego M, G6mez-Hernfindez A, Tufi6n J,

Hem丘ndez-Vargas B,別anco-Colio LM, Mas S, Aparicio C, Ortega L, Vivanco F, Gerique JG, Diaz C, Hernfindez G, Egido J. 2002; Atorvastatin reduces the expression of

cyclooxygenase-2 in a rabbit model ofatherosclerosis and in cultured vascular muscle cells.

Atherosclerosis. 160:49-58.

Jones PS, Savory R, Barratt P, Bell AR, Gray TJ, Jenkins NA, Gilbert DJ, Copeland NG, Bell DR. 1995; Chromosomal localisation, inducibility, tissue-specific expression and strain differences in three murine p eroxisome-proliferator-activated一一receptor genes. Eur J Biochem. 233:219-226.

Karin M.1995;The regulation of AP-1 activity by mitogen-activated proteln kinases. J Bio1 Chem.

270:16483-16486.

Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, Umesono K,

Evans RM. 1994; Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA. 91:7355-7359.

Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M. 199e; Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. A17ature 343:531-535

Lawn RM, VVade DP, Garvin MR, VVang X, Schwartz K, Porter JG, Seilhamer JJ, Vaughan AM, Oram JF. 1999; The Tangier disease gene product AB C I controls the cellular

apolipoprotein-mediated lipid removal pathway. 」 Clin lnvest. 104:R25-R3 1.

Lee H, Shi W, Tontonoz P, Wang S, Subbanagounder G, H:e面ck CC, Hama S, Borromeo C,

Evans RM, Berliner JA, Nagy L. 2000; Role for peroxisome proliferator-aetivated receptor ct in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. Circ Res. 87:516-521.

Lemberger T, Desvergne B, Wahh W.1996;Peroxisome proliferator一・activated receptors二a nuclear receptor signalihg pathway in lipid physiology. Annu Rev Celi Dev Biol. 12:335-363.

60

Li AC, Binder CJ, Gutierrez A, Brown KK, Plotkin CR, Pattison rw, VallederAF, Davis RA,

VVillson TM, Witztum皿、, Palinski W, Glass CK:.2004;Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARor, 6/6, and y. /Clin lnvest.

114二1564-1576.

Li AC, Brown KK, Silvestre MJ, ’VVillson TM, Palinski VV, Glass CK 2000; Peroxisome proliferator-activated receptor y ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J CIin lnvest. 106:523-531.

Matsumura T, Sakai M, Kobori S, Biwa T, Takemura T, Matsuda H, Hakamata H, Horiuchi S,

Shichiri M. 1997; Two intracellular signaling pathways for activation o£protein kinase C are involved in oxidized low-density lipoprotein-induced macrophage growth. Arterioscler 7hromb Vasc Biol. 17:3013-3020.

Matsumura T, Sakai M, Matsuda K, Furukawa N, Kaneko K, Shichiri M. 1999; Cis-acting DNA elements of mouse granulocyte/macrophage colony-stimulating factor gene responsive to oxidized low density lipoprotein. JBiol Chem. 274:37665-37672.

Matsuo T, Matsumura T, Sakai M, Senokuchi T, Yano M, Kiritoshi S, Sonoda K, Kukidome D,

Pestdl:RGβrownlee M, Nishikawa T, Araki E.2004;15d-PGJ2 inhibits oxidized LDレinduced

macrophage proliferation by inhibition of GM-CSF production via inactivation ofNF・一i〈B. Biochem Biophys Res Commun. 314:817-823.

Miyamoto T, Kaneko A, Kakizawa T, Yaj ima H, Kamijo K, Sekine R, Hiramatsu K, Nishii Y,

Hashimoto T, Hashizume K. 1997; lnhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor. Competitive binding to the response element. J Biol Chem.

272:7752-7758.

Munker R, Gasson J, Ogawa M, Koerner HP. 1986; Recombinant human TNF induces production of granulocyte-monocyte colony-stimulating factor. Nature. 323:79-82.

Nagy L, Tontonoz P, Alvarez JG Chen H, Evans RM. 1998 ; Oxidized LDL regulates macrophage gene expression through ligand activation of PPARy. Cell. 93:229d-240.

61

O’Brien K, Nagano Y, Gown A, Kita T, Chait A. 1991; Probucol treatment affects the cellular composition but not anti-oxidized low density lipoprotein immunoreactivity ofplaques from Watanabe heritable hyperlipidemic rabbits. Arterioscler 7]zromb 11:751-759

Ohlssonet BG Englund MC, Karlsson AL, Knutsen E, Erixon C, Skribeck H, Liu Y, Bondj ers G ’Wiklund O. 1996; Oxidized low density lipoprotein inhibits lipopolysaccharide-induced

binding of nuclear factor-icB to DNA and the subsequent expression oftumor necrosis factor-ct and interleukin-1P in macrophages. 」 Clin lnvest. 98:78-89.

Oram J[F, Lawn RM, Garvin MR, VVade DP.2000; ABCAI i s the cAMP-inducible apolipoprotein receptor that mediates cholesterol secretion from macrophages. J Biol Chem.

275:34508-34511.

Oram JF, Vaughan AM. 2000; ABCAI-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins, Curr Opin Lipidol. 11:253-260.

Palinski W, R.osenfeld EM, Yh-her伽ala S, Bu重ler WS, Par曲sarathy S, C繍rew ET,

Steinberg D, Witz加m LJ.1989:10w density lipoprotein undergoes oxidative modi丘cation in vivo.

Proc Natl A cad Sci USA. 86:1372-1376.

Pontsler AV, Hilaire AS, Marathe GK, Zimmerman GA, Mclntyre TM. 2002;

Cyclooxygenase-2 is induced in monocytes by peroxisome proliferator activated receptor y and oxidized alkyl phospholipids from oxidized low density lipoprotein. J Biol Chem.

277:13029-13036.

Ricote M, Huang J, Faj as L, Li A, VVelch J, Naj ib J, Witztum LJ, Auwerx J, Palinski W, Glass KC. 1998; Expression of the peroxisome proliferator-activated receptor y (PPARy) in human

atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low

density lipoprotein. Proc Natl A cad Sci USA. 95:7614-7619.

Rosenfeld ME, Ross R. 1990; Macrophage and smooth muscle cell proliferation in atherosclerotic lesions ofWHHL and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis

10:680-687

Ross R. 1999; Atherosclerosis-an inflammatory disease. N Engl JMed. 340:115-126.

62

Sakai M, Miyazaki A, Sakamoto Y, Shichiri M, Horiuchi S. 1992; Cross-linking of apolipoproteins is involved in a loss of the ligand activity ofhigh density lipoprotein upon Cu2’一mediated oxidation. FEBS Lett. 314:199-202.

Senokuchi T, Matsumura T, Sakai M, Matsuo T, Yano M, Kiritoshi S, Sonoda K, Kukidome D, Nishikawa T, Araki E. 2004; Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase mediate macrophage proliferation induced by oxidized low-density lipoprotein.

Atherosclerosis. 176:233-245.

Senokuchi T, Matsumura T, Sakai M, Yano’M, Taguchi T, Matsuo T, Sonoda K, Kukidome D,

Imote K, Nishikawa T, Kim-Mitsuyama S, Takuwa Y, Araki E. 2005; Statins suppress oxidized low一・density lipoprotein-induced macrophage proliferation by inactivation of small G protein-p38 MAPK pathway. J Biol Chem. 280:6627-6633.

Spagnoli LG Orlandi A, Santeusanio G 1991; Foam cells of the rabbit atherosclerotic plaque arrested in metaphase by colchicine show a macrophage phenotype. A therosclerosis 88:87-92

Steinberg I), Parthasarathy S, Carew TE, Khoo JC, Witztum皿、.1989;Beyond cholesterol.

Modifications of low-density lipoprotein that increase its atherogenicity. N Engl JMed.

320:915-924.

Takahashi N, Kawada T, Goto T, Yamamoto T, Taimatsu A, Matsui N, Kimura K, Saito M,

Hosokawa M, Miyashita K, Fushiki T. 2002; Dual action of isoprenols from herbal medicines on both PPARy and PPARct in 3 T3-L l adipocytes and HepG2 hepatocytes. FEBS lett. 514:3 15-322.

Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM. 1994 ; mPPARy2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. ;8:1224-1234.

Tontonoz P, Hu E, Spiegelman BM. 1994; Stimulation of adipogenesis in fibroblasts by PPARy2,

a lipid-activated transcription factor. Cell. 79:1147-1 156.

Tontonoz P, Nagy L, Alvarez JG Thomazy VA, Evans RM. 1998; PPARy promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 93:241-252.

63

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