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Patologia e fisiopatologia generale - nuclear receptos in macrophages

Appunti in inglese per il corso di Patologia e fisiopatologia generale della professoressa Castoria su nuclear receptos in macrophages: a link between metabolism and inflammation, lipid metabolism of lesion macrophages, coupling of the signaling events, inflammation in atherosclerosis.

Esame di Patologia e Fisiopatologia Generale docente Prof. G. Castoria

Anteprima

ESTRATTO DOCUMENTO

A. Szanto, T. R}

oszer / FEBS Letters 582 (2008) 106–116 111

PPAR-c has been implicated in several functions of DCs.

IL-1-b, IL-6 [132–134] and IL-12 [135]. IL-4 induces expression Activation of the receptor change the expression of co-stimula-

of PPAR-c [106] and according to our observations PPAR-c tory molecules on DCs with reduced capacity to induce lym-

signaling seems to be part of the anti-inflammatory response phocyte proliferation and inhibits migration by decreasing

by intensifying processes driven by IL-4 and mitigating IFN- MCP-2, CCR7, EBI1 ligand chemokine [161,162]. Activation

TNF-a-provoked pro-inflammatory reactions (Szanto

c-, of PPAR-c leads to reduced stimulation of DCs by TLR ago-

et al., unpublished data). nists [163]. Furthermore, PPAR-c

It was shown recently, that activation of LXR inhibits secre- via induction of retinoic

tion of pro-inflammatory molecules like inducible nitric oxide acid synthesis induces CD1d expression in DCs resulting in

synthase, IL-6, IL-1-b, TNF-a [23]. NKT cell proliferation and possibly altered lipid presentation

The anti-inflammatory cytokine IL-10 generates protective by CD1 molecules [164,165]. Absence of PPAR-c in DCs

signals against atherosclerosis shown in IL-10 deficient mice increases their immunogenicity [166]. LXR also alters DC phe-

by increased and in IL-10 transgenic mice by decreased lesion notype by decreasing IL-12, increasing IL-10 secretion and

formation [136–138]. 15d-PGJ blocking its T-cell stimulatory ability [167].

can inhibit IL-10 signaling in a

2 A recent study demonstrated that regulatory T-cells (Tregs)

STAT3 dependent and PPAR-c-independent way [139]. reduced atherosclerosis when transferred, while depletion of

Another anti-inflammatory cytokine, transforming growth +

these CD25 cells increased pathogenesis [168,169]. Transfer

factor (TGF-b) also inhibits atherosclerosis at several levels.

b of Tregs into ApoE knockout mice attenuates atherosclerosis

By inducing collagen synthesis it stabilizes the plaque and pre- [170]. PPAR-c-expressing, but not PPAR-c null Tregs were

vents formation of the vulnerable plaque. Patients with athero- shown to prevent colitis suggesting a role for PPAR-c in regu-

sclerosis have less active TGF-b in their sera [140]. Stimulating lating immune responses through Tregs [171].

TGF-b signaling in mice reduces the formation of fatty

streaks, whilst blocking it with neutralizing antibody acceler-

ates disease progression in ApoE-deficient mice [141].

PPAR-c agonists inhibit TGF-b-induced connective tissue 11. Perspectives

growth factor expression via Smad3 [142] or fibronectin PPARs and LXRs are known as ligand-regulated transcrip-

expression [143–145]. PPAR-c can repress TGF-b1 gene tion factors that play central regulatory roles in lipid uptake,

through induction of phosphatase and tensin homologue metabolism and efflux. Importantly, they are also implicated

deleted on chromosome 10 (PTEN) [146]. in the regulation of inflammatory reactions. PPARs and LXRs

Inflammatory processes at the lesion site elaborate growth fac- are activated by fatty acids, oxLDL, arachidonic acid metabo-

tors from macrophages, which stimulate smooth muscle cell pro- lites like eicosanoids, prostaglandins, leukotriens and oxidized

liferation and synthesis of extracellular matrix elements cholesterol, respectively. Majority of these natural ligands are

resulting in the formation of the fibrous cap. Narrowing of vessel derived from the metabolism of unsaturated fatty acids and

lumen and disruption of this plaque are the major sources of clin- cholesterol, therefore disorders of lipid consumption and

ical outcomes in atherosclerosis, such as angina pectoris, myo- processing can influence transcriptional activity of PPAR

cardial infarction and stroke. Destabilization of the fibrous and LXR-regulated genes. Here, we provided a synopsis of

cap is enhanced by secretion of matrix metalloproteinases how the regulation of lipid homeostasis and inflammation is

(MMPs), which are type IV collagenases and degrade collagens interlaced by macrophages within the artery wall during ath-

of extracellular matrix in mammals. MMPs were also shown to erogenesis. PPAR-c is an inflammatory mediator controlling

be expressed in atherosclerotic lesion at high level [147–153]. many aspects of the inflammatory program with a net anti-ath-

There is evidence to suggest that PPAR-c is capable of inhib- erogenic consequence. However we have to note that some of

iting extracellular matrix remodeling in fatty streaks. It inhibits the anti-inflammatory effects assigned to PPAR-c activators

expression of MMP-9 secretion [154,155]. Interestingly, LXR are receptor-independent and inflammatory processes posi-

can also repress MMP-9 expression [156]. These data suggest tively regulated by PPAR-c are still elusive. Much less is

that nuclear receptors regulate matrix degradation during late known about LXR in inflammation but based on our current

atherosclerosis and also inhibit the formation of vulnerable knowledge we can assume further important findings concern-

plaque and subsequently thrombosis. ing the role of LXR in DC and lymphocyte functions.

Although majority of PPAR- and LXR-induced cellular

10. Involvement of adaptive immune response in atherogenesis events result in anti-atherogenic processes, some effects are

predicted to be atherogenic at the early stage of atherogenesis.

Dendritic cells (DCs) are professional antigen-presenting Activation of PPARs and LXRs by exogenous ligands can be

cells derived from monocytes or other myeloid progenitors easily a ‘‘poison hath residence and medicine power’’, since it

and have been implicated in lesion progression. S-100 positive can result in multiple changes in gene expression profile of le-

DCs are present at lesion sites [157]. CCR7 the main chemo- sion macrophages and cells of the artery wall. Here, we should

kine receptor regulating DC migration is expressed in the refer to a very recent report on increased risk of myocardial

lesion [158]. Recently, a specific group of T-cells, natural killer infarction and risk of death from cardiovascular causes in pa-

T-cells (NKT-cells) have been detected in the atherosclerotic tients treated with a TZD, Rosiglitazone upon a meta-analysis

lesion. These cells are characterized by the expression of of previous studies. However, as the authors claim there were

Va14Ja281-containing T-cell receptor (TCR) and rec-

a-chains limitations of this analysis and further comprehensive studies

ognize lipid antigens presented by CD1d molecules. Lack of are required [172].

CD1d in ApoE null mice decreases atherosclerosis [159,160]. The main perspective of PPAR and LXR research is to elu-

This suggests a novel crosstalk between lipid molecules and cidate the biological activities of each receptor subtype to facil-

the immune system at the level of DC function. itate the development of selective PPAR and LXR modulators

112 A. Szanto, T. R}

oszer / FEBS Letters 582 (2008) 106–116

that exhibit improved pharmaceutical benefits in therapy of [17] Chen, Z. et al. (2001) Troglitazone inhibits atherosclerosis in

apolipoprotein E-knockout mice: pleiotropic effects on CD36

atherosclerosis and metabolic syndrome. Also a huge challenge expression and HDL. Arterioscler. Thromb. Vasc. Biol. 21, 372–377.

for the future is the characterization of the species-specificity of [18] Akiyama, T.E. et al. (2002) Conditional disruption of the

the identified processes, since many reported mechanisms are peroxisome proliferator-activated receptor gamma gene in mice

seemed to be human or murine-specific. Furthermore, macro- results in lowered expression of ABCA1, ABCG1, and apoE in

macrophages and reduced cholesterol efflux. Mol. Cell Biol. 22,

phage biology has also been shown to be more complex than 2607–2619.

previously thought. The identification of various monocyte [19] Babaev, V.R., Yancey, P.G., Ryzhov, S.V., Kon, V., Breyer,

subtypes, differently activated macrophage subsets and the M.D., Magnuson, M.A., Fazio, S. and Linton, M.F. (2005)

involvement of DCs in metabolic disorders predict that much Conditional knockout of macrophage PPARgamma increases

remained to be discovered in this field. atherosclerosis in C57BL/6 and low-density lipoprotein receptor-

deficient mice. Arterioscler. Thromb. Vasc. Biol. 25, 1647–1653.

[20] Willy, P.J., Umesono, K., Ong, E.S., Evans, R.M., Heyman,

Acknowledgements: The authors are grateful for L. Nagy for critical R.A. and Mangelsdorf, D.J. (1995) LXR, a nuclear receptor that

reading of the manuscript and for insightful discussions. A.Sz. is sup- defines a distinct retinoid response pathway. Genes Dev. 9,

ported by the Hungarian Academy of Sciences (Bolyai Scholarship) 1033–1045.

and by Grants from Hungarian Science Research Fund (OTKA/ [21] Repa, J.J. et al. (2000) Regulation of absorption and ABC1-

61814) and from the University of Debrecen (Mecenatura). T.R. is also mediated efflux of cholesterol by RXR heterodimers. Science

supported by the Hungarian Academy of Sciences. 289, 1524–1529.

[22] Fu, X., Menke, J.G., Chen, Y., Zhou, G., MacNaul, K.L.,

Wright, S.D., Sparrow, C.P. and Lund, E.G. (2001) 27-

References Hydroxycholesterol is an endogenous ligand for liver X receptor

in cholesterol-loaded cells. J. Biol. Chem. 276, 38378–38387.

[1] Gresham, G.A. and Howard, A.N. (1961) The histogenesis of [23] Joseph, S.B., Castrillo, A., Laffitte, B.A., Mangelsdorf, D.J. and

the atherosclerotic fatty streak. J. Atheroscler. Res. 1, 413–416. Tontonoz, P. (2003) Reciprocal regulation of inflammation and

[2] Haller, H. (1977) Epidermiology and associated risk factors of lipid metabolism by liver X receptors. Nat. Med. 9, 213–219.

hyperlipoproteinemia. Z. Gesamte Inn. Med. 32, 124–128. [24] Castrillo, A., Joseph, S.B., Vaidya, S.A., Haberland, M., Fogel-

[3] Lusis, A.J. (2000) Atherosclerosis. Nature 407, 233–241. man, A.M., Cheng, G. and Tontonoz, P. (2003) Crosstalk between

[4] Glass, C.K. and Witztum, J.L. (2001) Atherosclerosis. the road LXR and toll-like receptor signaling mediates bacterial and viral

ahead. Cell 104, 503–516. antagonism of cholesterol metabolism. Mol. Cell 12, 805–816.

[5] Skalen, K., Gustafsson, M., Rydberg, E.K., Hulten, L.M., [25] Peet, D.J., Janowski, B.A. and Mangelsdorf, D.J. (1998) The

Wiklund, O., Innerarity, T.L. and Boren, J. (2002) Subendothe- LXRs: a new class of oxysterol receptors. Curr. Opin. Genet.

lial retention of atherogenic lipoproteins in early atherosclerosis. Dev. 8, 571–575.

Nature 417, 750–754. [26] Laffitte, B.A., Joseph, S.B., Walczak, R., Pei, L., Wilpitz, D.C.,

[6] Quinn, M.T., Parthasarathy, S., Fong, L.G. and Steinberg, D. Collins, J.L. and Tontonoz, P. (2001) Autoregulation of the

(1987) Oxidatively modified low density lipoproteins: a potential human liver X receptor alpha promoter. Mol. Cell Biol. 21,

role in recruitment and retention of monocyte/macrophages 7558–7568.

during atherogenesis. Proc. Natl. Acad. Sci. USA 84, 2995–2998. [27] Claudel, T. et al. (2001) Reduction of atherosclerosis in apoli-

[7] Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C. and poprotein E knockout mice by activation of the retinoid X

Witztum, J.L. (1989) Beyond cholesterol. Modifications of low- receptor. Proc. Natl. Acad. Sci. USA 98, 2610–2615.

density lipoprotein that increase its atherogenicity. New Engl. J. [28] Joseph, S.B. et al. (2002) Synthetic LXR ligand inhibits the

Med. 320, 915–924. development of atherosclerosis in mice. Proc. Natl. Acad. Sci.

[8] Navab, M. et al. (1996) The Yin and Yang of oxidation in the USA 99, 7604–7609.

development of the fatty streak. A review based on the 1994 [29] Venkateswaran, A., Laffitte, B.A., Joseph, S.B., Mak, P.A.,

George Lyman Duff Memorial Lecture. Arterioscler. Thromb. Wilpitz, D.C., Edwards, P.A. and Tontonoz, P. (2000) Control

Vasc. Biol. 16, 831–842. of cellular cholesterol efflux by the nuclear oxysterol receptor

[9] Libby, P. (2002) Inflammation in atherosclerosis. Nature 420, LXR alpha. Proc. Natl. Acad. Sci. USA 97, 12097–12102.

868–874. [30] Bodzioch, M. et al. (1999) The gene encoding ATP-binding

[10] Hansson, G.K. and Libby, P. (2006) The immune response in cassette transporter 1 is mutated in Tangier disease. Nat. Genet.

atherosclerosis: a double-edged sword. Nat. Rev. Immunol. 6, 22, 347–351.

508–519. [31] Brooks-Wilson, A. et al. (1999) Mutations in ABC1 in Tangier

[11] Tontonoz, P., Nagy, L., Alvarez, J.G., Thomazy, V.A. and disease and familial high-density lipoprotein deficiency. Nat.

Evans, R.M. (1998) PPARgamma promotes monocyte/macro- Genet. 22, 336–345.

phage differentiation and uptake of oxidized LDL. Cell 93, 241– [32] Rust, S. et al. (1999) Tangier disease is caused by mutations in

252. the gene encoding ATP-binding cassette transporter 1. Nat.

[12] Ricote, M. et al. (1998) Expression of the peroxisome prolifer- Genet. 22, 352–355.

ator-activated receptor gamma (PPARgamma) in human ath- [33] Costet, P., Luo, Y., Wang, N. and Tall, A.R. (2000) Sterol-

erosclerosis and regulation in macrophages by colony dependent transactivation of the ABC1 promoter by the liver X

stimulating factors and oxidized low density lipoprotein. Proc. receptor/retinoid X receptor. J. Biol. Chem. 275, 28240–28245.

Natl. Acad. Sci. USA 95, 7614–7619. [34] Venkateswaran, A., Repa, J.J., Lobaccaro, J.M., Bronson, A.,

[13] Nagy, L., Tontonoz, P., Alvarez, J.G., Chen, H. and Evans, Mangelsdorf, D.J. and Edwards, P.A. (2000) Human white/

R.M. (1998) Oxidized LDL regulates macrophage gene expres- murine ABC8 mRNA levels are highly induced in lipid-loaded

sion through ligand activation of PPARgamma. Cell 93, 229– macrophages. A transcriptional role for specific oxysterols. J.

240. Biol. Chem. 275, 14700–14707.

[14] Chawla, A., Barak, Y., Nagy, L., Liao, D., Tontonoz, P. and [35] Repa, J.J., Berge, K.E., Pomajzl, C., Richardson, J.A., Hobbs,

Evans, R.M. (2001) PPAR-gamma dependent and independent H. and Mangelsdorf, D.J. (2002) Regulation of ATP-binding

effects on macrophage-gene expression in lipid metabolism and cassette sterol transporters ABCG5 and ABCG8 by the liver X

inflammation. Nat. Med. 7, 48–52. receptors alpha and beta. J. Biol. Chem. 277, 18793–18800.

[15] Chawla, A. et al. (2001) A PPAR gamma-LXR-ABCA1 path- [36] Salvayre, R., Auge, N., Benoist, H. and Negre-Salvayre, A.

way in macrophages is involved in cholesterol efflux and (2002) Oxidized low-density lipoprotein-induced apoptosis. Bio-

atherogenesis. Mol. Cell 7, 161–171. chim. Biophys. Acta 1585, 213–221.

[16] Li, A.C., Brown, K.K., Silvestre, M.J., Willson, T.M., Palinski, [37] Joseph, S.B. et al. (2004) LXR-dependent gene expression is

W. and Glass, C.K. (2000) Peroxisome proliferator-activated important for macrophage survival and the innate immune

receptor gamma ligands inhibit development of atherosclerosis response. Cell 119, 299–309.

in LDL receptor-deficient mice. J. Clin. Invest. 106, 523–531.

A. Szanto, T. R}

oszer / FEBS Letters 582 (2008) 106–116 113

[38] Valledor, A.F., Hsu, L.C., Ogawa, S., Sawka-Verhelle, D., liver X receptor alpha gene expression via an autoregulatory

Karin, M. and Glass, C.K. (2004) Activation of liver X receptors loop mechanism. Mol. Endocrinol. 16, 506–514.

and retinoid X receptors prevents bacterial-induced macrophage [58] Graham, T.L., Mookherjee, C., Suckling, K.E., Palmer, C.N.

apoptosis. Proc. Natl. Acad. Sci. USA 101, 17813–17818. and Patel, L. (2005) The PPARdelta agonist GW0742X reduces

[39] Arai, S. et al. (2005) A role for the apoptosis inhibitory factor atherosclerosis in LDLR( / ) mice. Atherosclerosis 181, 29–37.

AIM/Spalpha/Api6 in atherosclerosis development. Cell Metab. [59] Chawla, A. et al. (2003) PPARdelta is a very low-density

1, 201–213. lipoprotein sensor in macrophages. Proc. Natl. Acad. Sci. USA

[40] Janowski, B.A., Willy, P.J., Devi, T.R., Falck, J.R. and 100, 1268–1273.

Mangelsdorf, D.J. (1996) An oxysterol signalling pathway [60] Lee, C.H., Chawla, A., Urbiztondo, N., Liao, D., Boisvert,

mediated by the nuclear receptor LXR alpha. Nature 383, W.A., Evans, R.M. and Curtiss, L.K. (2003) Transcriptional

728–731. repression of atherogenic inflammation: modulation by PPAR-

[41] Janowski, B.A., Grogan, M.J., Jones, S.A., Wisely, G.B., delta. Science 302, 453–457.

Kliewer, S.A., Corey, E.J. and Mangelsdorf, D.J. (1999) [61] Lee, C.H., Kang, K., Mehl, I.R., Nofsinger, R., Alaynick, W.A.,

Structural requirements of ligands for the oxysterol liver X Chong, L.W., Rosenfeld, J.M. and Evans, R.M. (2006) Perox-

receptors LXRalpha and LXRbeta. Proc. Natl. Acad. Sci. USA isome proliferator-activated receptor delta promotes very low-

96, 266–271. density lipoprotein-derived fatty acid catabolism in the macro-

[42] Lehmann, J.M. et al. (1997) Activation of the nuclear receptor phage. Proc. Natl. Acad. Sci. USA 103, 2434–2439.

LXR by oxysterols defines a new hormone response pathway. J. [62] van der Veen, J.N. et al. (2005) Reduced cholesterol absorption

Biol. Chem. 272, 3137–3140. upon PPARdelta activation coincides with decreased intestinal

[43] Andersson, S., Davis, D.L., Dahlback, H., Jornvall, H. and expression of NPC1L1. J. Lipid Res. 46, 526–534.

Russell, D.W. (1989) Cloning, structure, and expression of the [63] Moore, K.J. et al. (2001) The role of PPAR-gamma in macro-

mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile phage differentiation and cholesterol uptake. Nat. Med. 7, 41–

acid biosynthetic enzyme. J. Biol. Chem. 264, 8222–8229. 47.

[44] Pikuleva, I.A., Babiker, A., Waterman, M.R. and Bjorkhem, I. [64] Crosby, M.B., Svenson, J.L., Zhang, J., Nicol, C.J., Gonzalez,

(1998) Activities of recombinant human cytochrome P450c27 F.J. and Gilkeson, G.S. (2005) Peroxisome proliferation-acti-

(CYP27) which produce intermediates of alternative bile acid vated receptor (PPAR)gamma is not necessary for synthetic

biosynthetic pathways. J. Biol. Chem. 273, 18153–18160. PPARgamma agonist inhibition of inducible nitric-oxide syn-

[45] Hulten, L.M., Lindmark, H., Diczfalusy, U., Bjorkhem, I., thase and nitric oxide. J. Pharmacol. Exp. Ther. 312, 69–76.

Ottosson, M., Liu, Y., Bondjers, G. and Wiklund, O. (1996) [65] Pascual, G. et al. (2005) A SUMOylation-dependent pathway

Oxysterols present in atherosclerotic tissue decrease the expres- mediates transrepression of inflammatory response genes by

sion of lipoprotein lipase messenger RNA in human monocyte- PPAR-gamma. Nature 437, 759–763.

derived macrophages. J. Clin. Invest. 97, 461–468. [66] Ghisletti, S., Huang, W., Ogawa, S., Pascual, G., Lin, M.E.,

[46] Crisby, M., Nilsson, J., Kostulas, V., Bjorkhem, I. and Diczf- Willson, T.M., Rosenfeld, M.G. and Glass, C.K. (2007) Parallel

alusy, U. (1997) Localization of sterol 27-hydroxylase immuno- SUMOylation-dependent pathways mediate gene- and signal-

reactivity in human atherosclerotic plaques. Biochim. Biophys. specific transrepression by LXRs and PPARgamma. Mol. Cell

Acta 1344, 278–285. 25, 57–70.

[47] Cali, J.J., Hsieh, C.L., Francke, U. and Russell, D.W. (1991) [67] Smith, J.D., Trogan, E., Ginsberg, M., Grigaux, C., Tian, J. and

Mutations in the bile acid biosynthetic enzyme sterol 27- Miyata, M. (1995) Decreased atherosclerosis in mice deficient in

hydroxylase underlie cerebrotendinous xanthomatosis. J. Biol. both macrophage colony-stimulating factor (op) and apolipo-

Chem. 266, 7779–7783. protein E. Proc. Natl. Acad. Sci. USA 92, 8264–8268.

[48] Bjorkhem, I. and Leitersdorf, E. (2000) Sterol 27-hydroxylase [68] de Villiers, W.J., Smith, J.D., Miyata, M., Dansky, H.M.,

deficiency: a rare cause of xanthomas in normocholesterolemic Darley, E. and Gordon, S. (1998) Macrophage phenotype in

humans. Trends Endocrinol. Metab. 11, 180–183. mice deficient in both macrophage-colony-stimulating factor

[49] Moghadasian, M.H., Salen, G., Frohlich, J.J. and Scudamore, (op) and apolipoprotein E. Arterioscler. Thromb. Vasc. Biol. 18,

C.H. (2002) Cerebrotendinous xanthomatosis: a rare disease 631–640.

with diverse manifestations. Arch. Neurol. 59, 527–529. [69] Wiktor-Jedrzejczak, W. and Gordon, S. (1996) Cytokine regu-

[50] Szanto, A. et al. (2004) Transcriptional regulation of human lation of the macrophage (M phi) system studied using the

CYP27 integrates retinoid, peroxisome proliferator-activated colony stimulating factor-1-deficient op/op mouse. Physiol. Rev.

receptor, and liver X receptor signaling in macrophages. Mol. 76, 927–947.

Cell Biol. 24, 8154–8166. [70] Ditiatkovski, M., Toh, B.H. and Bobik, A. (2006) GM-CSF

[51] Majdalawieh, A., Zhang, L., Fuki, I.V., Rader, D.J. and Ro, deficiency reduces macrophage PPAR-gamma expression and

H.S. (2006) Adipocyte enhancer-binding protein 1 is a potential aggravates atherosclerosis in ApoE-deficient mice. Arterioscler.

novel atherogenic factor involved in macrophage cholesterol Thromb. Vasc. Biol. 26, 2337–2344.

homeostasis and inflammation. Proc. Natl. Acad. Sci. USA 103, [71] Haghighat, A., Weiss, D., Whalin, M.K., Cowan, D.P. and

2346–2351. Taylor, W.R. (2007) Granulocyte colony-stimulating factor and

[52] Li, A.C. et al. (2004) Differential inhibition of macrophage granulocyte macrophage colony-stimulating factor exacerbate

foam-cell formation and atherosclerosis in mice by PPARalpha, atherosclerosis in apolipoprotein E-deficient mice. Circulation

beta/delta, and gamma. J. Clin. Invest. 114, 1564–1576. 115, 2049–2054.

[53] Rosen, H. et al. (1998) Markedly reduced bile acid synthesis but [72] Cybulsky, M.I. and Gimbrone Jr., M.A. (1991) Endothelial

maintained levels of cholesterol and vitamin D metabolites in expression of a mononuclear leukocyte adhesion molecule

mice with disrupted sterol 27-hydroxylase gene. J. Biol. Chem. during atherogenesis. Science 251, 788–791.

273, 14805–14812. [73] Johnson, R.C. et al. (1997) Absence of P-selectin delays fatty

[54] Repa, J.J., Lund, E.G., Horton, J.D., Leitersdorf, E., Russell, streak formation in mice. J. Clin. Invest. 99, 1037–1043.

[74] Dong, Z.M., Chapman, S.M., Brown, A.A., Frenette, P.S.,

D.W., Dietschy, J.M. and Turley, S.D. (2000) Disruption of the Hynes, R.O. and Wagner, D.D. (1998) The combined role of

sterol 27-hydroxylase gene in mice results in hepatomegaly and P- and E-selectins in atherosclerosis. J. Clin. Invest. 102, 145–

hypertriglyceridemia. Reversal by cholic acid feeding. J. Biol. 152.

Chem. 275, 39685–39692. [75] Cybulsky, M.I. et al. (2001) A major role for VCAM-1, but not

[55] Goodwin, B. et al. (2003) Identification of bile acid precursors ICAM-1, in early atherosclerosis. J. Clin. Invest. 107, 1255–1262.

as endogenous ligands for the nuclear xenobiotic pregnane X [76] Gu, L., Okada, Y., Clinton, S.K., Gerard, C., Sukhova, G.K.,

receptor. Proc. Natl. Acad. Sci. USA 100, 223–228. Libby, P. and Rollins, B.J. (1998) Absence of monocyte

[56] Whitney, K.D. et al. (2001) Liver X receptor (LXR) regulation chemoattractant protein-1 reduces atherosclerosis in low density

of the LXRalpha gene in human macrophages. J. Biol. Chem. lipoprotein receptor-deficient mice. Mol. Cell 2, 275–281.

276, 43509–43515. [77] Boring, L., Gosling, J., Cleary, M. and Charo, I.F. (1998)

[57] Li, Y., Bolten, C., Bhat, B.G., Woodring-Dietz, J., Li, S., Decreased lesion formation in CCR2 / mice reveals a role for

Prayaga, S.K., Xia, C. and Lala, D.S. (2002) Induction of human

114 A. Szanto, T. R}

oszer / FEBS Letters 582 (2008) 106–116

chemokines in the initiation of atherosclerosis. Nature 394, 894– [97] Febbraio, M., Guy, E. and Silverstein, R.L. (2004) Stem cell

897. transplantation reveals that absence of macrophage CD36 is

[78] Boisvert, W.A., Santiago, R., Curtiss, L.K. and Terkeltaub, protective against atherosclerosis. Arterioscler. Thromb. Vasc.

R.A. (1998) A leukocyte homologue of the IL-8 receptor CXCR- Biol. 24, 2333–2338.

2 mediates the accumulation of macrophages in atherosclerotic [98] Podrez, E.A. et al. (2000) Macrophage scavenger receptor CD36

lesions of LDL receptor-deficient mice. J. Clin. Invest. 101, 353– is the major receptor for LDL modified by monocyte-generated

363. reactive nitrogen species. J. Clin. Invest. 105, 1095–1108.

[79] Combadiere, C. et al. (2003) Decreased atherosclerotic lesion [99] Moore, K.J., Kunjathoor, V.V., Koehn, S.L., Manning, J.J.,

formation in CX3CR1/apolipoprotein E double knockout mice. Tseng, A.A., Silver, J.M., McKee, M. and Freeman, M.W.

Circulation 107, 1009–1016. (2005) Loss of receptor-mediated lipid uptake via scavenger

[80] Lesnik, P., Haskell, C.A. and Charo, I.F. (2003) Decreased receptor A or CD36 pathways does not ameliorate atheroscle-

atherosclerosis in CX3CR1 / mice reveals a role for fractal- rosis in hyperlipidemic mice. J. Clin. Invest. 115, 2192–2201.

kine in atherogenesis. J. Clin. Invest. 111, 333–340. [100] Braun, A. et al. (2002) Loss of SR-BI expression leads to the

[81] Lin, S.G., Yu, X.Y., Chen, Y.X., Huang, X.R., Metz, C., early onset of occlusive atherosclerotic coronary artery disease,

Bucala, R., Lau, C.P. and Lan, H.Y. (2000) De novo expression spontaneous myocardial infarctions, severe cardiac dysfunction,

of macrophage migration inhibitory factor in atherogenesis in and premature death in apolipoprotein E-deficient mice. Circ.

rabbits. Circ. Res. 87, 1202–1208. Res. 90, 270–276.

[82] Burger-Kentischer, A. et al. (2002) Expression of macrophage [101] Zhang, W., Yancey, P.G., Su, Y.R., Babaev, V.R., Zhang, Y.,

migration inhibitory factor in different stages of human athero- Fazio, S. and Linton, M.F. (2003) Inactivation of macrophage

sclerosis. Circulation 105, 1561–1566. scavenger receptor class B type I promotes atherosclerotic lesion

[83] Pan, J.H. et al. (2004) Macrophage migration inhibitory factor development in apolipoprotein E-deficient mice. Circulation 108,

deficiency impairs atherosclerosis in low-density lipoprotein 2258–2263.

receptor-deficient mice. Circulation 109, 3149–3153. [102] Van Eck, M., Bos, I.S., Hildebrand, R.B., Van Rij, B.T. and Van

[84] Bernhagen, J. et al. (2007) MIF is a noncognate ligand of CXC Berkel, T.J. (2004) Dual role for scavenger receptor class B, type

chemokine receptors in inflammatory and atherogenic cell I on bone marrow-derived cells in atherosclerotic lesion devel-

recruitment. Nat. Med. 13, 587–596. opment. Am. J. Pathol. 165, 785–794.

[85] Han, K.H., Chang, M.K., Boullier, A., Green, S.R., Li, A., [103] Michelsen, K.S. et al. (2004) Lack of Toll-like receptor 4 or

Glass, C.K. and Quehenberger, O. (2000) Oxidized LDL reduces myeloid differentiation factor 88 reduces atherosclerosis and

monocyte CCR2 expression through pathways involving perox- alters plaque phenotype in mice deficient in apolipoprotein E.

isome proliferator-activated receptor gamma. J. Clin. Invest. Proc. Natl. Acad. Sci. USA 101, 10679–10684.

106, 793–802. [104] Tobias, P. and Curtiss, L.K. (2005) Thematic review series: The

[86] Chen, Y., Green, S.R., Ho, J., Li, A., Almazan, F. and immune system and atherogenesis. Paying the price for pathogen

Quehenberger, O. (2005) The mouse CCR2 gene is regulated protection: toll receptors in atherogenesis. J. Lipid Res. 46, 404–

by two promoters that are responsive to plasma cholesterol and 411.

peroxisome proliferator-activated receptor gamma ligands. Bio- [105] Mullick, A.E., Tobias, P.S. and Curtiss, L.K. (2005) Modulation

chem. Biophys. Res. Commun. 332, 188–193. of atherosclerosis in mice by Toll-like receptor 2. J. Clin. Invest.

[87] Barlic, J., Zhang, Y., Foley, J.F. and Murphy, P.M. (2006) 115, 3149–3156.

Oxidized lipid-driven chemokine receptor switch, CCR2 to [106] Huang, J.T. et al. (1999) Interleukin-4-dependent production of

CX3CR1, mediates adhesion of human macrophages to coro- PPAR-gamma ligands in macrophages by 12/15-lipoxygenase.

nary artery smooth muscle cells through a peroxisome prolifer- Nature 400, 378–382.

ator-activated receptor gamma-dependent pathway. Circulation [107] Sato, O., Kuriki, C., Fukui, Y. and Motojima, K. (2002) Dual

114, 807–819. promoter structure of mouse and human fatty acid translocase/

[88] Shah, Y.M., Morimura, K. and Gonzalez, F.J. (2007) Expres- CD36 genes and unique transcriptional activation by peroxisome

sion of peroxisome proliferator-activated receptor-gamma in proliferator-activated receptor alpha and gamma ligands. J. Biol.

macrophage suppresses experimentally induced colitis. Am. J. Chem. 277, 15703–15711.

Physiol. Gastrointest. Liver Physiol. 292, G657–G666. [108] Ricote, M., Li, A.C., Willson, T.M., Kelly, C.J. and Glass, C.K.

[89] Gordon, S. (2002) Pattern recognition receptors: doubling up for (1998) The peroxisome proliferator-activated receptor-gamma is

the innate immune response. Cell 111, 927–930. a negative regulator of macrophage activation. Nature 391, 79–

[90] Shimaoka, T., Kume, N., Minami, M., Hayashida, K., Kataoka, 82.

H., Kita, T. and Yonehara, S. (2000) Molecular cloning of a [109] Chui, P.C., Guan, H.P., Lehrke, M. and Lazar, M.A. (2005)

novel scavenger receptor for oxidized low density lipoprotein, PPARgamma regulates adipocyte cholesterol metabolism via

SR-PSOX, on macrophages. J. Biol. Chem. 275, 40663–40666. oxidized LDL receptor 1. J. Clin. Invest. 115, 2244–2256.

[91] Suzuki, H. et al. (1997) A role for macrophage scavenger [110] Lehrke, M. et al. (2007) CXCL16 is a marker of inflammation,

receptors in atherosclerosis and susceptibility to infection. atherosclerosis, and acute coronary syndromes in humans. J.

Nature 386, 292–296. Am. Coll. Cardiol. 49, 442–449.

[92] Suzuki, H. et al. (1997) The multiple roles of macrophage [111] Frostegard, J., Ulfgren, A.K., Nyberg, P., Hedin, U., Sweden-

scavenger receptors (MSR) in vivo: resistance to atherosclerosis borg, J., Andersson, U. and Hansson, G.K. (1999) Cytokine

and susceptibility to infection in MSR knockout mice. J. expression in advanced human atherosclerotic plaques: domi-

Atheroscler. Thromb. 4, 1–11. nance of pro-inflammatory (Th1) and macrophage-stimulating

[93] Sakaguchi, H. et al. (1998) Role of macrophage scavenger cytokines. Atherosclerosis 145, 33–43.

receptors in diet-induced atherosclerosis in mice. Lab. Invest. 78, [112] Gupta, S., Pablo, A.M., Jiang, X., Wang, N., Tall, A.R. and

423–434. Schindler, C. (1997) IFN-gamma potentiates atherosclerosis in

ApoE knock-out mice. J. Clin. Invest. 99, 2752–2761.

[94] Babaev, V.R., Gleaves, L.A., Carter, K.J., Suzuki, H., Kodama, [113] Whitman, S.C., Ravisankar, P., Elam, H. and Daugherty, A.

T., Fazio, S. and Linton, M.F. (2000) Reduced atherosclerotic (2000) Exogenous interferon-gamma enhances atherosclerosis in

lesions in mice deficient for total or macrophage-specific apolipoprotein E / mice. Am. J. Pathol. 157, 1819–1824.

expression of scavenger receptor-A. Arterioscler. Thromb. Vasc. [114] Buono, C., Come, C.E., Stavrakis, G., Maguire, G.F., Connelly,

Biol. 20, 2593–2599. P.W. and Lichtman, A.H. (2003) Influence of interferon-gamma

[95] de Winther, M.P. et al. (1999) Scavenger receptor deficiency on the extent and phenotype of diet-induced atherosclerosis in

leads to more complex atherosclerotic lesions in APOE3Leiden the LDLR-deficient mouse. Arterioscler. Thromb. Vasc. Biol.

transgenic mice. Atherosclerosis 144, 315–321. 23, 454–460.

[96] Febbraio, M., Podrez, E.A., Smith, J.D., Hajjar, D.P., Hazen, [115] Laurat, E., Poirier, B., Tupin, E., Caligiuri, G., Hansson, G.K.,

S.L., Hoff, H.F., Sharma, K. and Silverstein, R.L. (2000) Bariety, J. and Nicoletti, A. (2001) In vivo downregulation of T

Targeted disruption of the class B scavenger receptor CD36 helper cell 1 immune responses reduces atherogenesis in apoli-

protects against atherosclerotic lesion development in mice. J. poprotein E-knockout mice. Circulation 104, 197–202.

Clin. Invest. 105, 1049–1056.


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Corso di laurea: Corso di laurea magistrale in medicina e chirurgia (ordinamento U.E. - durata 6 anni) (CASERTA, NAPOLI)
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I contenuti di questa pagina costituiscono rielaborazioni personali del Publisher valeria0186 di informazioni apprese con la frequenza delle lezioni di Patologia e Fisiopatologia Generale e studio autonomo di eventuali libri di riferimento in preparazione dell'esame finale o della tesi. Non devono intendersi come materiale ufficiale dell'università Seconda Università di Napoli SUN - Unina2 o del prof Castoria Gabriella.

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