Interleukin-10 protects against atherosclerosis by modulating multiple atherogenic macrophage function

Xinbing Han; William A. Boisvert

doi:10.1160/TH14-06-0509

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 113(03): 505-512
DOI: 10.1160/TH14-06-0509

Theme Issue Article

Schattauer GmbH

Interleukin-10 protects against atherosclerosis by modulating multiple atherogenic macrophage function

Xinbing Han

¹Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

,

William A. Boisvert

²Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA

³Kazan Federal University, Kazan, Russia

› Author Affiliations

Abstract

Summary

Atherosclerosis is primarily a disorder of lipid metabolism, but there is also a prominent chronic inflammatory component that drives the atherosclerotic lesion progression in the artery wall. During hyperlipidaemic conditions, there is a rapid influx of circulating monocytes into the atherosclerosis-prone areas of the arterial intima. These infiltrated monocytes differentiate into macrophages and take up the atherogenic lipoproteins in the intima of the vessel wall that have been modified within the lesion environment. Interleukin (IL)-10 is a prototypic anti-inflammatory cytokine made primarily by the macrophages and Th2 subtype T lymphocytes. In terms of atherosclerosis its major roles include inhibition of macrophage activation as well as inhibition of matrix metalloproteinase, pro-inflammatory cytokines and cyclooxygenase- 2 expression in lipid-loaded and activated macrophage foam cells. Recent discoveries suggest another important role of IL-10 in atherosclerosis: its ability to alter lipid metabolism in macrophages. The current review will highlight the present knowledge on multiple ways in which IL-10 mediates atherosclerosis. As macrophages play a critical role in all stages of atherosclerosis, the review will concentrate on how IL-10 regulates the activities of macrophages that are especially important in the development of atherosclerosis.

Full Text

References

References
1 Hansson GK, Robertson AK, Soderberg-Naucler C. Inflammation and atherosclerosis. Annu Rev Pathol 2006; 1: 297-329.
2 Moubayed SP, Heinonen TM, Tardif JC. Anti-inflammatory drugs and atherosclerosis. Curr Opin Lipidol 2007; 18: 638-644.
3 Charo IF, Taub R. Anti-inflammatory therapeutics for the treatment of atherosclerosis. Nat Rev Drug Discov 2011; 10: 365-376.
4 Little PJ, Chait A, Bobik A. Cellular and cytokine-based inflammatory processes as novel therapeutic targets for the prevention and treatment of atherosclerosis. Pharmacol Ther 2011; 131: 255-268.
5 Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473: 317-325.
6 Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340: 115-126.
7 Lusis AJ. Atherosclerosis. Nature 2000; 407: 233-241.
8 Wang N, Tall AR. Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arterioscler Thromb Vasc Biol 2003; 23: 1178-1184.
9 Brown MS, Goldstein JL. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 1983; 52: 223-261.
10 Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 2006; 86: 515-581.
11 Bobik A, Agrotis A, Kanellakis P. et al. Distinct patterns of transforming growth factor-beta isoform and receptor expression in human atherosclerotic lesions. Colocalisation implicates TGF-beta in fibrofatty lesion development. Circulation 1999; 99: 2883-2891.
12 Hansson GK. Immune mechanisms in atherosclerosis. Arterioscler Thromb Vasc Biol 2001; 21: 1876-1890.
13 Mallat Z, Heymes C, Ohan J. et al. Expression of interleukin-10 in advanced human atherosclerotic plaques: relation to inducible nitric oxide synthase expression and cell death. Arterioscler Thromb Vasc Biol 1999; 19: 611-616.
14 Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell 2011; 145: 341-355.
15 Uyemura K, Demer LL, Castle SC. et al. Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis. J Clin Invest 1996; 97: 2130-2138.
16 Heeschen C, Dimmeler S, Hamm CW. et al. Serum level of the antiinflammatory cytokine interleukin-10 is an important prognostic determinant in patients with acute coronary syndromes. Circulation 2003; 107: 2109-2114.
17 Ito T, Ikeda U. Inflammatory cytokines and cardiovascular disease. Curr Drug Targets Inflamm Allergy 2003; 2: 257-265.
18 Terkeltaub RA. IL-10: An “immunologic scalpel” for atherosclerosis?. Arterioscler Thromb Vasc Biol 1999; 19: 2823-2825.
19 Xavier MN, Winter MG, Spees AM. et al. CD4+ T cell-derived IL-10 promotes Brucella abortus persistence via modulation of macrophage function. PLoS Pa-thog 2013; 9: e1003454.
20 Wang P, Wu P, Siegel MI. et al. Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J Biol Chem 1995; 270: 9558-9563.
21 Kishore R, Tebo JM, Kolosov M. et al. Cutting edge: clustered AU-rich elements are the target of IL-10-mediated mRNA destabilisation in mouse macrophages. J Immunol 1999; 162: 2457-2461.
22 Boisvert WA, Santiago R, Curtiss LK. et al. A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 1998; 101: 353-363.
23 Zimmerman MA, Reznikov LL, Raeburn CD, Selzman CH. Interleukin-10 attenuates the response to vascular injury. J Surg Res 2004; 121: 206-213.
24 Han X, Kitamoto S, Lian Q. et al. Interleukin-10 facilitates both cholesterol uptake and efflux in macrophages. J Biol Chem 2009; 284: 32950-32958.
25 Han X, Kitamoto S, Wang H. et al. Interleukin-10 overexpression in macro-phages suppresses atherosclerosis in hyperlipidaemic mice. FASEB J 2010; 24: 2869-2880.
26 Nazari-Jahantigh M, Wei Y, Noels H. et al. MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages. J Clin Invest 2012; 122: 4190-4202.
27 McCoy CE, Sheedy FJ, Qualls JE. et al. IL-10 inhibits miR-155 induction by tolllike receptors. J Biol Chem 2010; 285: 20492-20498.
28 Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995; 91: 2844-2850.
29 Ardissino D, Merlini PA, Ariens R. et al. Tissue-factor antigen and activity in human coronary atherosclerotic plaques. Lancet 1997; 349: 769-771.
30 Kai H, Ikeda H, Yasukawa H. et al. Peripheral blood levels of matrix metallopro-teases-2 and -9 are elevated in patients with acute coronary syndromes. J Am Coll Cardiol 1998; 32: 368-372.
31 Caligiuri G, Rudling M, Ollivier V. et al. Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med 2003; 9: 10-17.
32 Gough PJ, Gomez IG, Wille PT. et al. Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. J Clin Invest 2006; 116: 59-69.
33 Boyle JJ. Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. Curr Vasc Pharmacol 2005; 3: 63-68.
34 Lemaitre V, O’Byrne TK, Borczuk AC. et al. ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis. J Clin Invest 2001; 107: 1227-1234.
35 Kong YZ, Huang XR, Ouyang X. et al. Evidence for vascular macrophage migration inhibitory factor in destabilisation of human atherosclerotic plaques. Cardiovasc Res 2005; 65: 272-282.
36 Kong YZ, Yu X, Tang JJ. et al. Macrophage migration inhibitory factor induces MMP-9 expression: implications for destabilisation of human atherosclerotic plaques. Atherosclerosis 2005; 178: 207-215.
37 Johnson JL, George SJ, Newby AC. et al. Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. Proc Natl Acad Sci USA 2005; 102: 15575-15580.
38 Holven KB, Halvorsen B, Bjerkeli V. et al. Impaired inhibitory effect of interleukin-10 on the balance between matrix metalloproteinase-9 and its inhibitor in mononuclear cells from hyperhomocysteinemic subjects. Stroke 2006; 37: 1731-1736.
39 Waehre T, Halvorsen B, Damas JK. et al. Inflammatory imbalance between IL-10 and TNFalpha in unstable angina potential plaque stabilizing effects of IL-10. Eur J Clin Invest 2002; 32: 803-810.
40 Kamimura M, Viedt C, Dalpke A. et al. Interleukin-10 suppresses tissue factor expression in lipopolysaccharide-stimulated macrophages via inhibition of Egr-1 and a serum response element/MEK-ERK1/2 pathway. Circ Res 2005; 97: 305-313.
41 Pajkrt D, van der Poll T, Levi M. et al. Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood 1997; 89: 2701-2705.
42 Amento EP, Ehsani N, Palmer H. et al. Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterioscler Thromb 1991; 11: 1223-1230.
43 Gallicchio M, Hufnagl P, Wojta J. et al. IFN-gamma inhibits thrombin- and endotoxin-induced plasminogen activator inhibitor type 1 in human endothelial cells. J Immunol 1996; 157: 2610-2617.
44 Cohen SB, Crawley JB, Kahan MC. et al. Interleukin-10 rescues T cells from apoptotic cell death: association with an upregulation of Bcl-2. Immunology 1997; 92: 1-5.
45 Minor Jr. RL, Myers PR, Guerra Jr. R. et al. Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. J Clin Invest 1990; 86: 2109-2116.
46 Witztum JL, Steinberg D. The oxidative modification hypothesis of atherosclerosis: does it hold for humans?. Trends Cardiovasc Med 2001; 11: 93-102.
47 Geng YJ, Wu Q, Muszynski M. et al. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Arterioscler Thromb Vasc Biol 1996; 16: 19-27.
48 Luoma JS, Stralin P, Marklund SL. et al. Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions: colocalisation with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins. Arterioscler Thromb Vasc Biol 1998; 18: 157-167.
49 Halvorsen B, Waehre T, Scholz H. et al. Interleukin-10 enhances the oxidized LDL-induced foam cell formation of macrophages by antiapoptotic mechanisms. J Lipid Res 2005; 46: 211-219.
50 Li Y, Zhang Y, Dorweiler B. et al. Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism. J Biol Chem 2008; 283: 34833-34843.
51 Rubic T, Lorenz RL. Downregulated CD36 and oxLDL uptake and stimulated ABCA1/G1 and cholesterol efflux as anti-atherosclerotic mechanisms of interleukin-10. Cardiovasc Res 2006; 69: 527-535.
52 Benoit M, Desnues B, Mege JL. Macrophage polarisation in bacterial infections. J Immunol 2008; 181: 3733-3739.
53 Mantovani A, Sica A, Locati M. Macrophage polarisation comes of age. Immunity 2005; 23: 344-346.
54 Martinez FO, Sica A, Mantovani A, Locati M. Macrophage activation and polarisation. Front Biosci 2008; 13: 453-461.
55 Boehler RM, Kuo R, Shin S. et al. Lentivirus delivery of IL-10 to promote and sustain macrophage polarisation towards an anti-inflammatory phenotype. Biotechnol Bioeng 2014; 111: 1210-1221.
56 Khallou-Laschet J, Varthaman A, Fornasa G. et al. Macrophage plasticity in experimental atherosclerosis. PLoS One 5: e8852.
57 Stoger JL, Gijbels MJ, van der Velden S. et al. Distribution of macrophage polarisation markers in human atherosclerosis. Atherosclerosis 2012; 225: 461-468.
58 van Tits LJ, Stienstra R, van Lent PL. et al. Oxidized LDL enhances pro-inflammatory responses of alternatively activated M2 macrophages: a crucial role for Kruppel-like factor 2. Atherosclerosis 2011; 214: 345-349.
59 El Hadri K, Mahmood DF, Couchie D. et al. Thioredoxin-1 promotes anti-inflammatory macrophages of the M2 phenotype and antagonizes atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32: 1445-1452.
60 Wolfs IM, Stoger JL, Goossens P. et al. Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens reduces murine atherosclerosis. FASEB J 2014; 28: 288-299.
61 Fei GZ, Huang YH, Swedenborg J. et al. Oxidised LDL modulates immune-activation by an IL-12 dependent mechanism. Atherosclerosis 2003; 169: 77-85.
62 Nagy L, Tontonoz P, Alvarez JG. et al. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 1998; 93: 229-240.
63 Kennedy MA, Barrera GC, Nakamura K. et al. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab 2005; 1: 121-131.
64 Ye D, Lammers B, Zhao Y. et al. ATP-binding cassette transporters A1 and G1, HDL metabolism, cholesterol efflux, and inflammation: important targets for the treatment of atherosclerosis. Curr Drug Targets 2011; 12: 647-660.
65 Zhao Y, Van Berkel TJ, Van Eck M. Relative roles of various efflux pathways in net cholesterol efflux from macrophage foam cells in atherosclerotic lesions. Curr Opin Lipidol 2010; 21: 441-453.
66 Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol 2011; 12: 204-212.
67 Moore KJ, Kunjathoor VV, Koehn SL. et al. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidaemic mice. J Clin Invest 2005; 115: 2192-2201.
68 Marleau S, Harb D, Bujold K. et al. EP 80317, a ligand of the CD36 scavenger receptor, protects apolipoprotein E-deficient mice from developing atherosclerotic lesions. FASEB J 2005; 19: 1869-1871.
69 Montoya D, Cruz D, Teles RM. et al. Divergence of macrophage phagocytic and antimicrobial programs in leprosy. Cell Host Microbe 2009; 6: 343-353.
70 Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 2010; 10: 36-46.
71 Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 2009; 27: 451-483.
72 Mallat Z, Besnard S, Duriez M. et al. Protective role of interleukin-10 in atherosclerosis. Circ Res 1999; 85: e17-24.
73 Pinderski Oslund LJ, Hedrick CC, Olvera T. et al. Interleukin-10 blocks atherosclerotic events in vitro and in vivo. Arterioscler Thromb Vasc Biol 1999; 19: 2847-2853.
74 Von Der Thusen JH, Kuiper J, Fekkes ML. et al. Attenuation of atherogenesis by systemic and local adenovirus-mediated gene transfer of interleukin-10 in LDLr-/- mice. FASEB J 2001; 15: 2730-2732.
75 Pinderski LJ, Fischbein MP, Subbanagounder G. et al. Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient Mice by altering lymphocyte and macrophage phenotypes. Circ Res 2002; 90: 1064-1071.
76 Namiki M, Kawashima S, Yamashita T. et al. Intramuscular gene transfer of interleukin-10 cDNA reduces atherosclerosis in apolipoprotein E-knockout mice. Atherosclerosis 2004; 172: 21-29.
77 Yoshioka T, Okada T, Maeda Y. et al. Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice. Gene Ther 2004; 11: 1772-1779.
78 Liu Y, Li D, Chen J. et al. Inhibition of atherogenesis in LDLR knockout mice by systemic delivery of adeno-associated virus type 2-hIL-10. Atherosclerosis 2006; 188: 19-27.
79 Du L, Dronadula N, Tanaka S. et al. Helper-Dependent Adenoviral Vector Achieves Prolonged, Stable Expression of Interleukin-10 in Rabbit Carotid Arteries but Does Not Limit Early Atherogenesis. Hum Gene Ther 2011; 22: 959-968.
80 Sun J, Li X, Feng H. et al. Magnetic resonance imaging of bone marrow cell-mediated interleukin-10 gene therapy of atherosclerosis. PLoS One 2011; 6: e24529.
81 Lee TS, Yen HC, Pan CC. et al. The role of interleukin 12 in the development of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 1999; 19: 734-742.
82 Eefting D, Schepers A, De Vries MR. et al. The effect of interleukin-10 knockout and overexpression on neointima formation in hypercholesterolemic APOE*3-Leiden mice. Atherosclerosis 2007; 193: 335-342.
83 Zhou X, Paulsson G, Stemme S. et al. Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice. J Clin Invest 1998; 101: 1717-1725.
84 Moore KW, de Waal Malefyt R, Coffman RL. et al. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683-765.
85 Selzman CH, McIntyre Jr. RC, Shames BD. et al. Interleukin-10 inhibits human vascular smooth muscle proliferation. J Mol Cell Cardiol 1998; 30: 889-896.
86 Mazighi M, Pelle A, Gonzalez W. et al. IL-10 inhibits vascular smooth muscle cell activation in vitro and in vivo. Am J Physiol Heart Circ Physiol 2004; 287: H866-871.
87 Dammanahalli JK, Wang X, Sun Z. Genetic interleukin-10 deficiency causes vascular remodelling via the upregulation of Nox1. J Hypertens 2011; 29: 2116-2125.
88 Zernecke A, Liehn EA, Gao JL. et al. Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10. Blood 2006; 107: 4240-4243.
89 Delleuze V, Scherman D, Bureau MF. Interleukin-10 expression after intramuscular DNA electrotransfer: kinetic studies. Biochem Biophys Res Commun 2002; 299: 29-34