Toll-like Receptor Signaling Pathways in Cardiovascular Diseases: Challenges and Opportunities

REFERENCES

• Arumugam TV, Okun E, Tang SC, Thundyil J, Taylor SM, Woodruff TM. Toll-like receptors in ischemia-reperfusion injury. Shock. 2009;32:4–16.
   PubMed Web of Science ®Google Scholar
• Rezaei N. Therapeutic targeting of pattern-recognition receptors. Int Immunopharmacol. 2006;6:863–869.
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med. 2007;13:460–469.
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. TLR signaling. Semin Immunol. 2007;19:24–32.
   PubMed Web of Science ®Google Scholar
• Hornung V, Barchet W, Schlee M, Hartmann G. RNA recognition via TLR7 and TLR8. Handb Exp Pharmacol. 2008;183:71–86.
   Google Scholar
• Krieg AM, Vollmer J. Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity. Immunol Rev. 2007;220:251–269.
   PubMed Web of Science ®Google Scholar
• Hedayat M, Takeda K, Rezaei N. Prophylactic and therapeutic implications of toll-like receptor ligands. Med Res Rev. 2012;32:294–325.
   PubMed Web of Science ®Google Scholar
• Horner AA, Redecke V, Raz E. Toll-like receptor ligands: hygiene, atopy and therapeutic implications. Curr Opin Allergy Clin Immunol. 2004;4:555–561.
   PubMed Web of Science ®Google Scholar
• Doughty LA, Carlton S, Galen B, Cooma-Ramberan I, Chung CS, Ayala A. Activation of common antiviral pathways can potentiate inflammatory responses to septic shock. Shock. 2006;26:187–194.
   PubMedGoogle Scholar
• Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008;42:145–151.
   PubMed Web of Science ®Google Scholar
• Blander JM. Phagocytosis and antigen presentation: a partnership initiated by Toll-like receptors. Ann Rheum Dis. 2008;67 (Suppl 3):iii44–iii49.
   PubMedGoogle Scholar
• Chao W, Shen Y, Zhu X, Lipopolysaccharide improves cardiomyocyte survival and function after serum deprivation. J Biol Chem. 2005;280:21997–2005.
   PubMed Web of Science ®Google Scholar
• Hodgkinson CP, Ye S. Toll-like receptors, their ligands, and atherosclerosis. ScientificWorldJournal. 2011;11:437–453.
   PubMedGoogle Scholar
• Chang EJ, Kim HJ, Ha J, Hyaluronan inhibits osteoclast differentiation via Toll-like receptor 4. J Cell Sci. 2007;120:166–176.
   PubMed Web of Science ®Google Scholar
• Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol. 2001;167:2887–2894.
   PubMed Web of Science ®Google Scholar
• Okamura Y, Watari M, Jerud ES, The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem. 2001;276:10229–10233.
   PubMed Web of Science ®Google Scholar
• Funderburg N, Lederman MM, Feng Z, Human β-defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci U S A. 2007;104:18631–18635.
   PubMed Web of Science ®Google Scholar
• Yu M, Wang H, Ding A, HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock. 2006;26:174–179.
   PubMed Web of Science ®Google Scholar
• Johnson GB, Brunn GJ, Kodaira Y, Platt JL. Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J Immunol. 2002;168:5233–5239.
   PubMed Web of Science ®Google Scholar
• Cohen-Sfady M, Nussbaum G, Pevsner-Fischer M, Heat shock protein 60 activates B cells via the TLR4-MyD88 pathway. J Immunol. 2005;175:3594–3602.
   PubMed Web of Science ®Google Scholar
• Tsan MF, Gao B. Endogenous ligands of Toll-like receptors. J Leukoc Biol. 2004;76:514–519.
   PubMed Web of Science ®Google Scholar
• Asea A, Rehli M, Kabingu E, Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem. 2002;277:15028–15034.
   PubMed Web of Science ®Google Scholar
• Chen K, Huang J, Gong W, Iribarren P, Dunlop NM, Wang JM. Toll-like receptors in inflammation, infection and cancer. Int Immunopharmacol. 2007;7:1271–1285.
   PubMed Web of Science ®Google Scholar
• Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol. 2006;177:1272–1281.
   PubMed Web of Science ®Google Scholar
• Dybdahl B, Wahba A, Lien E, Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through toll-like receptor-4. Circulation. 2002;105: 685–690.
   PubMed Web of Science ®Google Scholar
• Lin WJ, Yeh WC. Implication of Toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock. 2005;24:206–209.
   PubMed Web of Science ®Google Scholar
• Cole JE, Georgiou E, Monaco C. The expression and functions of toll-like receptors in atherosclerosis. Mediators Inflamm. 2010;2010:3939–3946.
   Google Scholar
• Hedayat M, Netea MG, Rezaei N. Targeting of Toll-like receptors: a decade of progress in combating infectious diseases. Lancet Infect Dis. 2011;11:702–712.
   PubMed Web of Science ®Google Scholar
• Chao W. Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart. Am J Physiol Heart Circ Physiol. 2009;296:H1–H12.
   PubMed Web of Science ®Google Scholar
• Meyer T, Stockfleth E. Clinical investigations of Toll-like receptor agonists. Expert Opin Investig Drugs. 2008;17:1051–1065.
   PubMed Web of Science ®Google Scholar
• Kaisho T, Akira S. Toll-like receptor function and signaling. J Allergy Clin Immunol. 2006;117:979–987; quiz 88.
   PubMed Web of Science ®Google Scholar
• Terrell AM, Crisostomo PR, Wairiuko GM, Wang M, Morrell ED, Meldrum DR. Jak/STAT/SOCS signaling circuits and associated cytokine-mediated inflammation and hypertrophy in the heart. Shock. 2006;26:226–234.
   PubMedGoogle Scholar
• Fan H, Peck OM, Tempel GE, Halushka PV, Cook JA. Toll-like receptor 4 coupled GI protein signaling pathways regulate extracellular signal-regulated kinase phosphorylation and AP-1 activation independent of NFkappaB activation. Shock. 2004;22:57–62.
   PubMedGoogle Scholar
• Gilliet M, Cao W, Liu YJ. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol. 2008;8:594–606.
   PubMed Web of Science ®Google Scholar
• Heinz S, Haehnel V, Karaghiosoff M, Species-specific regulation of Toll-like receptor 3 genes in men and mice. J Biol Chem. 2003;278:21502–509.
   PubMed Web of Science ®Google Scholar
• Lin E, Freedman JE, Beaulieu LM. Innate immunity and toll-like receptor antagonists: a potential role in the treatment of cardiovascular diseases. Cardiovasc Ther. 2009;27:117–123.
   PubMedGoogle Scholar
• Nian M, Lee P, Khaper N, Liu P. Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res. 2004;94:1543–1553.
   PubMed Web of Science ®Google Scholar
• Thurman JM. Triggers of inflammation after renal ischemia/reperfusion. Clin Immunol. 2007;123:7–13.
   PubMed Web of Science ®Google Scholar
• Zingarelli B, Hake PW, Mangeshkar P, Diverse cardioprotective signaling mechanisms of peroxisome proliferator-activated receptor-gamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone, in reperfusion injury: role of nuclear factor-kappaB, heat shock factor 1, and Akt. Shock. 2007;28:554–563.
   PubMedGoogle Scholar
• Rivo J, Zeira E, Galun E, Einav S, Linden J, Matot I. Attenuation of reperfusion lung injury and apoptosis by A2A adenosine receptor activation is associated with modulation of Bcl-2 and Bax expression and activation of extracellular signal-regulated kinases. Shock. 2007;27: 266–273.
   PubMed Web of Science ®Google Scholar
• Shernan SK, Collard CD. Role of the complement system in ischaemic heart disease: potential for pharmacological intervention. BioDrugs. 2001;15:595–607.
   PubMedGoogle Scholar
• Hwang MW, Matsumori A, Furukawa Y, Neutralization of interleukin-1beta in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling. J Am Coll Cardiol. 2001;38:1546–1553.
   PubMed Web of Science ®Google Scholar
• Giugliano GR, Giugliano RP, Gibson CM, Kuntz RE. Meta-analysis of corticosteroid treatment in acute myocardial infarction. Am J Cardiol. 2003;91:1055–1059.
   PubMed Web of Science ®Google Scholar
• Bujak M, Dobaczewski M, Chatila K, Interleukin-1 receptor type I signaling critically regulates infarct healing and cardiac remodeling. Am J Pathol. 2008;173:57–67.
   PubMed Web of Science ®Google Scholar
• Levonen AL, Vahakangas E, Koponen JK, Yla-Herttuala S. Antioxidant gene therapy for cardiovascular disease: current status and future perspectives. Circulation. 2008;117:2142–2150.
   Google Scholar
• Hsu SF, Niu KC, Lin CL, Lin MT. Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke. Shock. 2006;26:210–220.
   PubMed Web of Science ®Google Scholar
• Hausenloy DJ, Yellon DM. The mitochondrial permeability transition pore: its fundamental role in mediating cell death during ischaemia and reperfusion. J Mol Cell Cardiol. 2003;35:339–341.
   PubMed Web of Science ®Google Scholar
• Prech M, Marszalek A, Schroder J, Apoptosis as a mechanism for the elimination of cardiomyocytes after acute myocardial infarction. Am J Cardiol. 2010;105:1240–1245.
   PubMedGoogle Scholar
• Wu Y, Yin X, Wijaya C, Huang MH, McConnell BK. Acute myocardial infarction in rats. J Vis Exp. 2011;48:e2464.
   Google Scholar
• Vanlangenakker N, Vanden Berghe T, Krysko DV, Festjens N, Vandenabeele P. Molecular mechanisms and pathophysiology of necrotic cell death. Curr Mol Med. 2008;8:207–220.
   PubMed Web of Science ®Google Scholar
• Lavrik IN. [Regulation of death receptor-induced apoptosis induced via CD95/FAS and other death receptors]. Mol Biol (Mosk). 2011;45:173–179.
   PubMedGoogle Scholar
• Arumugam TV, Chan SL, Jo DG, Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nat Med. 2006;12:621–623.
   PubMed Web of Science ®Google Scholar
• Frantz S, Kobzik L, Kim YD, Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest. 1999;104:271–280.
   PubMed Web of Science ®Google Scholar
• Roy SK, Srivastava RK, Shankar S. Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J Mol Signal. 2010;5:10.
   PubMedGoogle Scholar
• Fang Y, Hu J. Toll-like receptor and its roles in myocardial ischemic/reperfusion injury. Med Sci Monit. 2011;17:RA100–RA109.
   PubMedGoogle Scholar
• Israel A. The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb Perspect Biol. 2010;2:a000158.
   PubMed Web of Science ®Google Scholar
• Ha T, Hua F, Liu X, Lipopolysaccharide-induced myocardial protection against ischaemia/reperfusion injury is mediated through a PI3K/Akt-dependent mechanism. Cardiovasc Res. 2008;78:546–553.
   PubMed Web of Science ®Google Scholar
• Shimamoto A, Chong AJ, Yada M, Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia–reperfusion injury. Circulation. 2006;114:I270–I274.
   PubMed Web of Science ®Google Scholar
• Shishido T, Nozaki N, Yamaguchi S, Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction. Circulation. 2003;108:2905–2910.
   PubMed Web of Science ®Google Scholar
• Favre J, Musette P, Douin-Echinard V, Toll-like receptors 2-deficient mice are protected against postischemic coronary endothelial dysfunction. Arterioscler Thromb Vasc Biol. 2007;27:1064–1071.
   PubMed Web of Science ®Google Scholar
• Arslan F, Smeets MB, O'Neill LA, Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-Toll-like receptor-2 antibody. Circulation. 2010;121:80–90.
   PubMed Web of Science ®Google Scholar
• Mersmann J, Koch A, Tran N, Toll-like receptor 2 signaling triggers fatal arrhythmias upon myocardial ischemia-reperfusion. Crit Care Med. 2010;38:1927–1932.
   PubMedGoogle Scholar
• Frantz S, Kelly RA, Bourcier T. Role of TLR-2 in the activation of nuclear factor kappaB by oxidative stress in cardiac myocytes. J Biol Chem. 2001;276:5197–5203.
   PubMed Web of Science ®Google Scholar
• Zhu X, Bagchi A, Zhao H, Toll-like receptor 2 activation by bacterial peptidoglycan-associated lipoprotein activates cardiomyocyte inflammation and contractile dysfunction. Crit Care Med. 2007;35:886–892.
   PubMed Web of Science ®Google Scholar
• Hua F, Ha T, Ma J, Blocking the MyD88-dependent pathway protects the myocardium from ischemia/reperfusion injury in rat hearts. Biochem Biophys Res Commun. 2005;338:1118–1125.
   PubMed Web of Science ®Google Scholar
• Feng Y, Zhao H, Xu X, Innate immune adaptor MyD88 mediates neutrophil recruitment and myocardial injury after ischemia–reperfusion in mice. Am J Physiol Heart Circ Physiol. 2008;295:H1311–H1318.
   Google Scholar
• Chao W. Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart. Am J Physiol Heart Circ Physiol. 2009;296:1–12.
   PubMed Web of Science ®Google Scholar
• Dong JW, Vallejo JG, Tzeng HP, Thomas JA, Mann DL. Innate immunity mediates myocardial preconditioning through Toll-like receptor 2 and TIRAP-dependent signaling pathways. Am J Physiol Heart Circ Physiol. 2010;298:H1079–H1087.
   PubMed Web of Science ®Google Scholar
• Oppenheim JJ, Yang D. Alarmins: chemotactic activators of immune responses. Curr Opin Immunol. 2005;17:359–365.
   PubMed Web of Science ®Google Scholar
• Yao YW, Zhang GH, Zhang YY, Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-kappaB. Cell Stress Chaperones. 2011;16:287–296.
   PubMedGoogle Scholar
• Schneider-Poetsch T, Ju J, Eyler DE, Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol. 2010;6:209–217.
   PubMed Web of Science ®Google Scholar
• Zhu X, Zhao H, Graveline AR, MyD88 and NOS2 are essential for Toll-like receptor 4-mediated survival effect in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2006;291:H1900–H1909.
   Web of Science ®Google Scholar
• Wang Y, Guo Y, Zhang SX, Ischemic preconditioning upregulates inducible nitric oxide synthase in cardiac myocyte. J Mol Cell Cardiol. 2002;34:5–15.
   PubMedGoogle Scholar
• Maejima Y, Adachi S, Morikawa K, Ito H, Isobe M. Nitric oxide inhibits myocardial apoptosis by preventing caspase-3 activity via S-nitrosylation. J Mol Cell Cardiol. 2005;38:163–174.
   PubMed Web of Science ®Google Scholar
• Yan ZQ, Hansson GK. Innate immunity, macrophage activation, and atherosclerosis. Immunol Rev. 2007;219:187–203.
   PubMed Web of Science ®Google Scholar
• Erridge C, Burdess A, Jackson AJ, Vascular cell responsiveness to Toll-like receptor ligands in carotid atheroma. Eur J Clin Invest. 2008;38:713–720.
   PubMed Web of Science ®Google Scholar
• Ott SJ, El Mokhtari NE, Musfeldt M, Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease. Circulation. 2006;113:929–937.
   PubMed Web of Science ®Google Scholar
• Laman JD, Schoneveld AH, Moll FL, van Meurs M, Pasterkamp G. Significance of peptidoglycan, a proinflammatory bacterial antigen in atherosclerotic arteries and its association with vulnerable plaques. Am J Cardiol. 2002;90:119–123.
   PubMed Web of Science ®Google Scholar
• Wick G, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol. 2004;22:361–403.
   PubMed Web of Science ®Google Scholar
• Ngeh J, Anand V, Gupta S. Chlamydia pneumoniae and atherosclerosis—what we know and what we don't. Clin Microbiol Infect. 2002;8:2–13.
   PubMed Web of Science ®Google Scholar
• Chen S, Sorrentino R, Shimada K, Chlamydia pneumoniae-induced foam cell formation requires MyD88-dependent and -independent signaling and is reciprocally modulated by liver X receptor activation. J Immunol. 2008;181:7186–7193.
   PubMed Web of Science ®Google Scholar
• Cao F, Castrillo A, Tontonoz P, Re F, Byrne GI. Chlamydia pneumoniae-induced macrophage foam cell formation is mediated by Toll-like receptor 2. Infect Immun. 2007;75:753–759.
   PubMed Web of Science ®Google Scholar
• Michelsen KS, Wong MH, Shah PK, Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci U S A. 2004;101:10679–10684.
   PubMed Web of Science ®Google Scholar
• Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ. Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation. 2002;105: 1158–1161.
   PubMed Web of Science ®Google Scholar
• Chang ZL. Important aspects of Toll-like receptors, ligands and their signaling pathways. Inflamm Res. 2010;59:791–808.
   PubMed Web of Science ®Google Scholar
• Su X, Ao L, Shi Y, Johnson TR, Fullerton DA, Meng X. Oxidized low density lipoprotein induces bone morphogenetic protein-2 in coronary artery endothelial cells via Toll-like receptors 2 and 4. J Biol Chem. 2011;286:12213–12220.
   PubMed Web of Science ®Google Scholar
• Shuang C, Wong MH, Schulte DJ, Arditi M, Michelsen KS. Differential expression of Toll-like receptor 2 (TLR2) and responses to TLR2 ligands between human and murine vascular endothelial cells. J Endotoxin Res. 2007;13:281–296.
   PubMedGoogle Scholar
• Curtiss LK, Tobias PS. Emerging role of Toll-like receptors in atherosclerosis. J Lipid Res. 2009;50 (Suppl):S340–S345.
   Google Scholar
• Muzio M, Bosisio D, Polentarutti N, Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol. 2000;164:5998–6004.
   PubMed Web of Science ®Google Scholar
• Kadowaki N, Ho S, Antonenko S, Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J Exp Med. 2001;194:863–869.
   PubMed Web of Science ®Google Scholar
• Visintin A, Mazzoni A, Spitzer JH, Wyllie DH, Dower SK, Segal DM. Regulation of Toll-like receptors in human monocytes and dendritic cells. J Immunol. 2001;166:249–255.
   PubMed Web of Science ®Google Scholar
• Hornung V, Rothenfusser S, Britsch S, Quantitative expression of Toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol. 2002;168:4531–4537.
   PubMed Web of Science ®Google Scholar
• Geng HL, Lu HQ, Zhang LZ, Increased expression of Toll like receptor 4 on peripheral-blood mononuclear cells in patients with coronary arteriosclerosis disease. Clin Exp Immunol. 2006;143:269–273.
   PubMed Web of Science ®Google Scholar
• Kuwahata S, Fujita S, Orihara K, High expression level of Toll-like receptor 2 on monocytes is an important risk factor for arteriosclerotic disease. Atherosclerosis. 2010;209:248–254.
   PubMed Web of Science ®Google Scholar
• Ashida K, Miyazaki K, Takayama E, Characterization of the expression of TLR2 (Toll-like receptor 2) and TLR4 on circulating monocytes in coronary artery disease. J Atheroscler Thromb. 2005;12:53–60.
   PubMed Web of Science ®Google Scholar
• Versteeg D, Hoefer IE, Schoneveld AH, Monocyte Toll-like receptor 2 and 4 responses and expression following percutaneous coronary intervention: association with lesion stenosis and fractional flow reserve. Heart. 2008;94:770–776.
   PubMed Web of Science ®Google Scholar
• Holvoet P, Davey PC, De Keyzer D, Oxidized low-density lipoprotein correlates positively with Toll-like receptor 2 and interferon regulatory factor-1 and inversely with superoxide dismutase-1 expression: studies in hypercholesterolemic swine and THP-1 cells. Arterioscler Thromb Vasc Biol. 2006;26:1558–1565.
   PubMed Web of Science ®Google Scholar
• Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004;63:582–592.
   PubMed Web of Science ®Google Scholar
• Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006;83:456S–460S.
   PubMed Web of Science ®Google Scholar
• Hodgkinson CP, Laxton RC, Patel K, Ye S. Advanced glycation end-product of low density lipoprotein activates the Toll-like 4 receptor pathway implications for diabetic atherosclerosis. Arterioscler Thromb Vasc Biol. 2008;28:2275–2281.
   PubMedGoogle Scholar
• Misciagna G, Logroscino G, De Michele G, Glycated apolipoprotein B and myocardial infarction. Nutr Metab Cardiovasc Dis. 2007;17:6–12.
   PubMedGoogle Scholar
• Stewart CR, Stuart LM, Wilkinson K, CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010;11:155–161.
   PubMed Web of Science ®Google Scholar
• Leitinger N. Oxidized phospholipids as modulators of inflammation in atherosclerosis. Curr Opin Lipidol. 2003;14:421–30.
   PubMed Web of Science ®Google Scholar
• Binder CJ, Shaw PX, Chang MK, The role of natural antibodies in atherogenesis. J Lipid Res. 2005;46:1353–1363.
   PubMed Web of Science ®Google Scholar
• Berliner JA, Watson AD. A role for oxidized phospholipids in atherosclerosis. N Engl J Med. 2005;353:9–11.
   PubMed Web of Science ®Google Scholar
• Berliner JA, Watson AD. A role for oxidized phospholipids in atherosclerosis. N Engl J Med. 2005;353:9–11.
   PubMed Web of Science ®Google Scholar
• Berliner JA, Leitinger N, Tsimikas S. The role of oxidized phospholipids in atherosclerosis. J Lipid Res. 2009;50 (Suppl):S207–S212.
   PubMedGoogle Scholar
• Harkewicz R, Hartvigsen K, Almazan F, Dennis EA, Witztum JL, Miller YI. Cholesteryl ester hydroperoxides are biologically active components of minimally oxidized low density lipoprotein. J Biol Chem. 2008;283:10241–10251.
   PubMedGoogle Scholar
• Miller YI, Viriyakosol S, Worrall DS, Boullier A, Butler S, Witztum JL. Toll-like receptor 4-dependent and -independent cytokine secretion induced by minimally oxidized low-density lipoprotein in macrophages. Arterioscler Thromb Vasc Biol. 2005;25:1213–1219.
   PubMed Web of Science ®Google Scholar
• Bae YS, Lee JH, Choi SH, Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: Toll-like receptor 4- and spleen tyrosine kinase-dependent activation of NADPH oxidase 2. Circ Res. 2009;104:210–218, 21p following 8.
   PubMed Web of Science ®Google Scholar
• Choi SH, Harkewicz R, Lee JH, Lipoprotein accumulation in macrophages via toll-like receptor-4-dependent fluid phase uptake. Circ Res. 2009;104:1355–1363.
   PubMed Web of Science ®Google Scholar
• Miller YI, Worrall DS, Funk CD, Feramisco JR, Witztum JL. Actin polymerization in macrophages in response to oxidized LDL and apoptotic cells: role of 12/15-lipoxygenase and phosphoinositide 3-kinase. Mol Biol Cell. 2003;14:4196–4206.
   PubMed Web of Science ®Google Scholar
• Kalinina N, Agrotis A, Antropova Y, Increased expression of the DNA-binding cytokine HMGB1 in human atherosclerotic lesions: role of activated macrophages and cytokines. Arterioscler Thromb Vasc Biol. 2004;24:2320–2325.
   PubMed Web of Science ®Google Scholar
• Hodgkinson CP, Patel K, Ye S. Functional Toll-like receptor 4 mutations modulate the response to fibrinogen. Thromb Haemost. 2008;100:301–307.
   PubMed Web of Science ®Google Scholar
• Lee JY, Ye J, Gao Z, Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. J Biol Chem. 2003;278:37041–37051.
   PubMed Web of Science ®Google Scholar
• Weatherill AR, Lee JY, Zhao L, Lemay DG, Youn HS, Hwang DH. Saturated and polyunsaturated fatty acids reciprocally modulate dendritic cell functions mediated through TLR4. J Immunol. 2005;174:5390–5397.
   PubMed Web of Science ®Google Scholar
• Nowak JZ. [Anti-inflammatory pro-resolving derivatives of omega-3 and omega-6 polyunsaturated fatty acids]. Postepy Hig Med Dosw (Online). 2010;64:115–132.
   PubMedGoogle Scholar
• Midwood K, Sacre S, Piccinini AM, Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med. 2009;15: 774–780.
   PubMed Web of Science ®Google Scholar
• Taylor KR, Gallo RL. Glycosaminoglycans and their proteoglycans: host-associated molecular patterns for initiation and modulation of inflammation. FASEB J. 2006;20:9–22.
   PubMed Web of Science ®Google Scholar
• Mullick AE, Tobias PS, Curtiss LK. Modulation of atherosclerosis in mice by Toll-like receptor 2. J Clin Invest. 2005;115:3149–3156.
   PubMed Web of Science ®Google Scholar
• Xu XH, Shah PK, Faure E, Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL. Circulation. 2001;104:3103–3108.
   PubMed Web of Science ®Google Scholar
• Mullick AE, Soldau K, Kiosses WB, Bell TA 3rd, Tobias PS, Curtiss LK. Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events. J Exp Med. 2008;205:373–383.
   PubMed Web of Science ®Google Scholar
• Monaco C, Gregan SM, Navin TJ, Foxwell BM, Davies AH, Feldmann M. Toll-like receptor-2 mediates inflammation and matrix degradation in human atherosclerosis. Circulation. 2009;120:2462–2469.
   PubMed Web of Science ®Google Scholar
• Liu X, Ukai T, Yumoto H, Toll-like receptor 2 plays a critical role in the progression of atherosclerosis that is independent of dietary lipids. Atherosclerosis. 2008;196:146–154.
   PubMed Web of Science ®Google Scholar
• Kawakami A, Osaka M, Aikawa M, Toll-like receptor 2 mediates apolipoprotein CIII-induced monocyte activation. Circ Res. 2008;103:1402–1409.
   PubMed Web of Science ®Google Scholar
• Hoebe K, Georgel P, Rutschmann S, CD36 is a sensor of diacylglycerides. Nature. 2005;433:523–527.
   PubMed Web of Science ®Google Scholar
• Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007;7:179–190.
   PubMed Web of Science ®Google Scholar
• Kim S, Takahashi H, Lin WW, Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009;457:102–106.
   PubMed Web of Science ®Google Scholar
• Caron G, Duluc D, Fremaux I, Direct stimulation of human T cells via TLR5 and TLR7/8: flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4+ T cells. J Immunol. 2005;175:1551–1557.
   PubMed Web of Science ®Google Scholar
• Komai-Koma M, Jones L, Ogg GS, Xu D, Liew FY. TLR2 is expressed on activated T cells as a costimulatory receptor. Proc Natl Acad Sci U S A. 2004;101:3029–3034.
   PubMed Web of Science ®Google Scholar
• Wesch D, Beetz S, Oberg HH, Marget M, Krengel K, Kabelitz D. Direct costimulatory effect of TLR3 ligand poly(I:C) on human gamma delta T lymphocytes. J Immunol. 2006;176:1348–1354.
   PubMed Web of Science ®Google Scholar
• Lee JG, Lim EJ, Park DW, Lee SH, Kim JR, Baek SH. A combination of Lox-1 and Nox1 regulates TLR9-mediated foam cell formation. Cell Signal. 2008;20:2266–2275.
   PubMed Web of Science ®Google Scholar
• Doyle SE, O'Connell RM, Miranda GA, Toll-like receptors induce a phagocytic gene program through p38. J Exp Med. 2004;199:81–90.
   PubMed Web of Science ®Google Scholar
• Castrillo A, Joseph SB, Vaidya SA, Crosstalk between LXR and Toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol Cell. 2003;12:805–816.
   PubMed Web of Science ®Google Scholar
• Joseph SB, Castrillo A, Laffitte BA, Mangelsdorf DJ, Tontonoz P. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med. 2003;9:213–219.
   PubMed Web of Science ®Google Scholar
• Wagner M, Poeck H, Jahrsdoerfer B, IL-12p70-dependent Th1 induction by human B cells requires combined activation with CD40 ligand and CpG DNA. J Immunol. 2004;172:954–963.
   PubMed Web of Science ®Google Scholar
• Agrawal S, Agrawal A, Doughty B, Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol. 2003;171:4984–4989.
   PubMed Web of Science ®Google Scholar
• Manicassamy S, Ravindran R, Deng J, Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat Med. 2009;15:401–409.
   PubMed Web of Science ®Google Scholar
• Mallat Z, Gojova A, Brun V, Induction of a regulatory T cell type 1 response reduces the development of atherosclerosis in apolipoprotein E-knockout mice. Circulation. 2003;108:1232–1237.
   PubMed Web of Science ®Google Scholar
• Gulen MF, Kang Z, Bulek K, The receptor SIGIRR suppresses Th17 cell proliferation via inhibition of the interleukin-1 receptor pathway and mTOR kinase activation. Immunity. 2010;32:54–66.
   PubMed Web of Science ®Google Scholar
• Yu CF, Peng WM, Oldenburg J, Human plasmacytoid dendritic cells support Th17 cell effector function in response to TLR7 ligation. J Immunol. 2010;184:1159–1167.
   PubMed Web of Science ®Google Scholar
• Chou MY, Fogelstrand L, Hartvigsen K, Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J Clin Invest. 2009;119:1335–1349.
   PubMed Web of Science ®Google Scholar
• Grimm M, Kim M, Rosenwald A, Toll-like receptor (TLR) 7 and TLR8 expression on CD133+ cells in colorectal cancer points to a specific role for inflammation-induced TLRs in tumourigenesis and tumour progression. Eur J Cancer. 2010;46:2849–2857.
   PubMed Web of Science ®Google Scholar
• Liu H, Komai-Koma M, Xu D, Liew FY. Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T cells. Proc Natl Acad Sci U S A. 2006;103:7048–7053.
   PubMed Web of Science ®Google Scholar
• Hasan U, Chaffois C, Gaillard C, Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J Immunol. 2005;174:2942–2950.
   PubMed Web of Science ®Google Scholar
• Cai Z, Shi Z, Sanchez A, Transcriptional regulation of Tlr11 gene expression in epithelial cells. J Biol Chem. 2009;284:33088–33096.
   PubMedGoogle Scholar