Top

Journal of Clinical Immunology

Published in:

01-07-2009

TLR4 Polymorphisms and Ageing: Implications for the Pathophysiology of Age-Related Diseases

Authors: Carmela Rita Balistreri, Giuseppina Colonna-Romano, Domenico Lio, Giuseppina Candore, Calogero Caruso

Published in: Journal of Clinical Immunology | Issue 4/2009

Abstract

Introduction

Innate immunity provides a first line of host defense against infection by recognizing and killing microbes while simultaneously activating an instructive immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition and function mainly by detection of pathogen-associated molecular patterns that do not exist in the host. Recognition of their ligands leads to a series of signaling events resulting in acute host responses, involved in killing pathogens.

Discussion

We describe the involvement of TLR4 polymorphisms in ageing, and in particular in age-related diseases, suggesting the crucial role of molecules of innate immunity in pathophysiology of these diseases. Hence, we observed that pro-inflammatory alleles may be related to unsuccessful ageing, such as Alzheimer’s disease, prostate cancer, and atherosclerosis; in contrast, the control of inflammation by anti-inflammatory alleles may result in increased longevity and successful ageing. Finally, a possible therapeutic approach to delay age-related diseases is outlined.

De Benedictis G, Franceschi C. The unusual genetics of human longevity. Sci Aging Knowledge Environ. 2006;2006(10):pe20. doi:10.1126/sageke.2006.10.pe20.PubMed

Salvioli S, Olivieri F, Marchegiani F, Cardelli M, Santoro A, Bellavista E, et al. Genes, ageing and longevity in humans: problems, advantages and perspectives. Free Radic Res. 2006;40:1303–23. doi:10.1080/10715760600917136.PubMed

Ostan R, Bucci L, Capri M, Salvioli S, Scurti M, Pini E, et al. Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation. 2008;15:224–40. doi:10.1159/000156466.PubMed

Candore G, Balistreri CR, Listì F, Grimaldi MP, Vasto S, Colonna-Romano G, et al. Immunogenetics, gender, and longevity. Ann N Y Acad Sci. 2006;1089:516–37. doi:10.1196/annals.1386.051.PubMed

Candore G, Colonna-Romano G, Balistreri CR, Di Carlo D, Grimaldi MP, Listì F, et al. Biology of longevity: role of the innate immune system. Rejuvenation Res. 2006;9:143–8. doi:10.1089/rej.2006.9.143.PubMed

Candore G, Balistreri CR, Colonna-Romano G, Grimaldi MP, Lio D, Listi' F, et al. Immunosenescence and anti-immunosenescence therapies: the case of probiotics. Rejuvenation Res. 2008;11:425–32. doi:10.1089/rej.2008.0662.PubMed

Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A. Human immunosenescence: is it infectious? Immunol Rev. 2005;205:257–68. doi:10.1111/j.0105-2896.2005.00271.PubMed

Pawelec G, Derhovanessian E, Larbi A, Strindhall J, Wikby A. Cytomegalovirus and human immunosenescence. Rev Med Virol. 2009;19:47–56. doi:10.1002/rmv.598.PubMed

Aw D, Silva AB, Palmer DB. Immunosenescence: emerging challenges for an ageing population. Immunology. 2007;120:435–46. doi:10.1111/j.1365-2567.2007.02555.x.PubMed

10.

Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol. 2007;211:144–56. doi:10.1002/path.2104.PubMed

11.

Troen BR. The biology of aging. Mt Sinai J Med. 2003;70:3–22.PubMed

12.

Franceschi C, Motta L, Motta M, Malaguarnera M, Capri M, Vasto S, et al. IMUSCE. The extreme longevity: the state of the art in Italy. Exp Gerontol. 2008;43:45–52. doi:10.1016/j.exger.2007.06.006.PubMed

13.

Capri M, Salvioli S, Monti D, Caruso C, Candore G, Vasto S, et al. Human longevity within an evolutionary perspective: the peculiar paradigm of a post-reproductive genetics. Exp Gerontol. 2008;43:53–60. doi:10.1016/j.exger.2007.06.004.PubMed

14.

Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP, et al. Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev. 2007;128:83–91. doi:10.1016/j.mad.2006.11.015.PubMed

15.

Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol. 2004;39:687–99. doi:10.1016/j.exger.2004.01.009.PubMed

16.

Kumagai Y, Takeuchi O, Akira S. Pathogen recognition by innate receptors. J Infect Chemother. 2008;14:86–92. doi:10.1007/s10156-008-0596-1.PubMed

17.

Takeuchi O, Akira S. Innate immunity to virus infection. Immunol Rev. 2009;227:75–86. doi:10.1111/j.1600-065X.2008.00737.x.PubMed

18.

Uematsu S, Akira S. Toll-like receptors (TLRs) and their ligands. Handb Exp Pharmacol. 2008;183:1–20. doi:10.1007/978-3-540-72167-3_1.PubMed

19.

Blander JM. Phagocytosis and antigen presentation: a partnership initiated by Toll-like receptors. Ann Rheum Dis. 2008;67(Suppl 3):iii44–9. doi:10.1136/ard.2008.097964.PubMed

20.

Netea MG, van de Veerdonk FL, Kullberg BJ, Van der Meer JW, Joosten LA. The role of NLRs and TLRs in the activation of the inflammasome. Expert Opin Biol Ther. 2008;8:1867–72. doi:10.1517/14712590802494212.PubMed

21.

Richards S, Watanabe C, Santos L, Craxton A, Clark EA. Regulation of B-cell entry into the cell cycle. Immunol Rev. 2008;224:183–200. doi:10.1111/j.1600-065X.2008.00652.x.PubMed

22.

Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008;42:145–51. doi:10.1016/j.cyto.2008.01.006.PubMed

23.

Hashimoto C, Hudson KL, Anderson KV. The Toll gene of Drosophila, required for dorsal–ventral embryonic polarity, appears to encode a transmembrane protein. Cell. 1988;29(52):269–79.

24.

Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388:394–7. doi:10.1038/41131.PubMed

25.

Tsan MF, Gao B. Endogenous ligands of Toll-like receptors. J Leukoc Biol. 2004;76:514–9. doi:10.1189/jlb.0304127.PubMed

26.

Zeytun A, van Velkinburgh JC, Pardington PE, Cary RR, Gupta G. Pathogen-specific innate immune response. Adv Exp Med Biol. 2007;598:342–57. doi:10.1007/978-0-387-71767-8_24.PubMed

27.

Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol. 2007;19:3–10. doi:org/10.1016/j.smim.2006.12.002.PubMed

28.

Ku C-L, Yang K, Bustamante J, Puel A, von Bernuth H, Santos OF, et al. Inherited disorders of human Toll-like receptor signaling: Immunological implications. Immunol Rev. 2005;203:10–20. doi:10.1111/j.0105-2896.2005.00235.x.PubMed

29.

Balistreri CR, Candore G, Colonna-Romano G, Grimaldi MP, Lio D, Listì F, et al. Role of TLR polymorphisms in immunosenescence. In: Fulop T, editor. Handbook on Immunosenescence. Netherlands: Springer; 2009. p. 659–70. doi:10.1007/978-1-4020-9062-2_1.

30.

van Duin D, Shaw AC. Toll-like receptors in older adults. J Am Geriatr Soc. 2007;55:1438–44. doi:10.1111/j.1532-5415.2007.01300.x.PubMed

31.

Bruunsgaard H, Pedersen BK. Age-related inflammatory cytokines and disease. Immunol Allergy Clin North Am. 2003;23:15–39. doi:10.1016/S0889-8561(02)00056-5.PubMed

32.

Rink L, Cakman I, Kirchner H. Altered cytokine production in the elderly. Mech Ageing Dev. 1998;102:199–209. doi:10.1016/S0047-6374(97)00153-X.PubMed

33.

Fulop T, Larbi A, Douziech N, Fortin C, Guérard KP, Lesur O, et al. Signal transduction and functional changes in neutrophils with aging. Aging Cell. 2004;3:217–26. doi:10.1111/j.1474-9728.2004.00110.x.PubMed

34.

van Duin D, Mohanty S, Thomas V, Ginter S, Montgomery RR, Fikrig E, et al. Age-associated defect in human TLR-1/2 function. J Immunol. 2007;178:970–5.PubMed

35.

Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54. doi:10.1111/j.1749-6632.2000.tb06651.x.PubMedCrossRef

36.

Agrawal A, Agrawal S, Gupta S. Dendritic cells in human aging. Exp Gerontol. 2007;42:421–6. doi:0.1007/s10875-007-9127-6.PubMed

37.

Rea IM, Candore G, Cavalloni L, Franceschi C, Colonna-Romano G, Lio D, et al. Longevity. In: Vandenbroeck K, editor. Cytokine gene polymorphisms in multifactorial conditions. Florida: CRC; 2006. p. 379–94. ISBN 9780849336195.

38.

van Duin D, Allore HG, Mohanty S, Ginter S, Newman FK, Belshe RB, et al. Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults. J Infect Dis. 2007;195:1590–7. doi:10.1086/516788.PubMed

39.

Smirnova I, Poltorak A, Chan EK, McBride C, Beutler B. Phylogenetic variation and polymorphism at the toll-like receptor 4 locus (TLR4). Genome Biol. 2000;1(1):RESEARCH002.1–RESEARCH002.10.

40.

Mushegian A, Medzhitov R. Evolutionary perspective on innate immune recognition. J Cell Biol. 2001;155:705–10. doi:10.1083/jcb.200107040.PubMed

41.

Ferwerda B, McCall MB, Alonso S, Giamarellos-Bourboulis EJ, Mouktaroudi M, Izagirre N, et al. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc Natl Acad Sci U S A. 2007;104:16645–50. doi:10.1073/pnas.0704828104.PubMed

42.

Ferwerda B, McCall MB, Verheijen K, Kullberg BJ, van der Ven AJ, Van der Meer JW, et al. Functional consequences of toll-like receptor 4 polymorphisms. Mol Med. 2008;14:346–52. doi:10.2119/2007-00135.PubMed

43.

Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000;25:187–91. doi:10.1038/76048.PubMed

44.

Balistreri CR, Candore G, Listì F, Fazio T, Gangi S, Incalcaterra E, et al. Role of TLR4 polymorphisms in inflammatory responses: implications for unsuccessful aging. Ann N Y Acad Sci. 2007;1119:203–7. doi:10.1196/annals.1404.003.PubMed

45.

Vasto S, Candore G, Listì F, Balistreri CR, Colonna-Romano G, Malavolta M, et al. Inflammation, genes and zinc in Alzheimer's disease. Brain Res Brain Res Rev. 2008;58:96–105. doi:10.1016/j.brainresrev.2007.12.001.

46.

Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer's disease. Neurobiol Aging. 2000;21:383–421. doi:10.1016/S0197-4580(00)00124-X.PubMed

47.

Streit WJ, Miller KR, Lopes KO, Njie E. Microglial degeneration in the aging brain—bad news for neurons? Front Biosci. 2008;13:3423–38. doi:10.2741/2937.PubMed

48.

Fassbender K, Walter S, Kühl S, Landmann R, Ishii K, Bertsch T, et al. The LPS receptor (CD14) links innate immunity with Alzheimer's disease. FASEB J. 2004;18:203–5. doi:10.1096/fj.03-0364fje.PubMed

49.

Tang SC, Lathia JD, Selvaraj PK, Jo DG, Mughal MR, Cheng A, et al. Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal. Exp Neurol. 2008;213:114–21. doi:10.1016/j.expneurol.2008.05.014.PubMed

50.

Bsibsi M, Ravid R, Gveric D, van Noort JM. Broad expression of Toll-like receptors in the human central nervous system. J Neuropathol Exp Neurol. 2002;61:1013–21.PubMed

51.

Finch CE, Morgan TE. Systemic inflammation, infection, ApoE alleles, and Alzheimer disease: a position paper. Curr Alzheimer Res. 2007;4:185–9. doi:10.2174/156720507780362254.PubMed

52.

Candore G, Balistreri CR, Grimaldi MP, Listì F, Vasto S, Chiappelli M, et al. Polymorphisms of pro-inflammatory genes and Alzheimer’s disease risk: a pharmacogenomic approach. Mech Ageing Dev. 2007;128:67–75. doi:10.1016/j.mad.2006.11.013.PubMed

53.

Minoretti P, Gazzaruso C, Vito CD, Emanuele E, Bianchi M, Coen E, et al. Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer's disease. Neurosci Lett. 2006;391:147–9. doi:10.1016/j.neulet.2005.08.047.PubMed

54.

Balistreri CR, Grimaldi MP, Chiappelli M, Licastro F, Castiglia L, Listì F, et al. Association between the polymorphisms of TLR4 and CD14 genes and Alzheimer's disease. Curr Pharm Des. 2008;14:2672–7. doi:10.2174/138161208786264089.PubMed

55.

Huang B, Zhao J, Li H, He KL, Chen Y, Chen SH, et al. Toll like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 2005;65:5009–14. doi:10.1158/0008-5472.CAN-05-0784.PubMed

56.

Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, et al. TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006;66:3859. doi:10.1158/0008-5472.CAN-05-3948.PubMed

57.

De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;7:256–69. doi:10.1038/nrc2090.PubMed

58.

Vasto S, Carruba G, Lio D, Colonna-Romano G, Di Bona D, Candore G, et al. Inflammation, ageing and cancer. Mech Ageing Dev. 2009;130:40–5. doi:10.1016/j.mad.2008.06.003.PubMed

59.

Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004;118:285–96. doi:10.1016/j.cell.2004.07.013.PubMed

60.

Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5:749–59. doi:10.1038/nri1703.PubMed

61.

van Maren WW, Jacobs JF, de Vries IJ, Nierkens S, Adema GJ. Toll-like receptor signalling on Tregs: to suppress or not to suppress? Immunology. 2008;124:445–52. doi:10.1111/j.1365-2567.2008.02871.x.PubMed

62.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96. doi:10.3322/CA.2007.0010.PubMed

63.

Nelson WG, De Marzo AM, Isaacs WB. Prostate cancer. N Engl J Med. 2003;24(349):366–81.

64.

Sardana G, Dowell B, Diamandis EP. Emerging biomarkers for the diagnosis and prognosis of prostate cancer. Clin Chem. 2008;54:1951–60. doi:10.1373/clinchem.2008.110668.PubMed

65.

Caruso C, Balistreri CR, Candore G, Carruba G, Colonna-Romano G, Di Bon AD, et al. Polymorphisms of pro-inflammatory genes and prostate cancer risk: a pharmacogenomic approach. Cancer Immunol Immunother. 2009. doi:10.1007/s00262-009-0658-y.

66.

Zheng SL, Augustsson-Bälter K, Chang B, Hedelin M, Li L, Adami HO, et al. Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the Cancer Prostate in Sweden Study. Cancer Res. 2004;64:2918–22. doi:10.1158/0008-5472.CAN-03-3280.PubMed

67.

Chen YC, Giovannucci E, Lazarus R, Kraft P, Ketkar S, Hunter DJ. Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer. Cancer Res. 2005;65:11771–8. doi:10.1158/0008-5472.CAN-05-2078.PubMed

68.

Cheng I, Plummer SJ, Casey G, Witte JS. Toll-like receptor 4 genetic variation and advanced prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16:352–5. doi:10.1158/1055-9965.EPI-06-0429.PubMed

69.

Balistreri CR, Caruso C, Carruba G, Miceli V, Campisi I, Lio D, Colonna-Romano G. F. Listì F,Candore G. A pilot study on prostate cancer risk and pro-inflammatory genotypes: pathophysiology and therapeutic implications. Curr Pharm Des. 2009. (in press).

70.

Vink A, de Kleijn DP, Pasterkamp G. Functional role for toll-like receptors in atherosclerosis and arterial remodeling. Curr Opin Lipidol. 2004;15:515–21. doi:10.1097/00041433-200410000-00004.PubMed

71.

Pasterkamp G, Van Keulen JK, De Kleijn DP. Role of Toll-like receptor 4 in the initiation and progression of atherosclerotic disease. Eur J Clin Invest. 2004;34:328–34. doi:10.1111/j.1365-2362.2004.01338.x.PubMed

72.

Bjorkbacka H. Multiple roles of Toll-like receptor signaling in atherosclerosis. Curr Opin Lipidol. 2006;17:527–33.PubMedCrossRef

73.

Mullick AE, Tobias PS, Curtiss LK. Toll-like receptors and atherosclerosis: key contributors in disease and health? Immunol Res. 2006;34:193–209. doi:10.1385/IR:34:3:193.PubMed

74.

Frantz S, Ertl G, Bauersachs J. Mechanisms of disease: Toll-like receptors in cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2007;4:444–54. doi:10.1038/ncpcardio0938.PubMed

75.

Stoll LL, Denning GM, Weintraub NL. Endotoxin, TLR4 signaling and vascular inflammation: potential therapeutic targets in cardiovascular disease. Curr Pharm Des. 2006;12:4229–45. doi:10.2174/138161206778743501.PubMed

76.

Kiechl S, Lorenz E, Reindl M, Wiedermann CJ, Oberhollenzer F, Bonora E, et al. Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med. 2002;347:185–92. doi:10.1056/NEJMoa012673.PubMed

77.

Netea MG, Hijmans A, van Wissen S, Smilde TJ, Trip MD, Kullberg BJ, et al. Toll-like receptor-4 Asp299Gly polymorphism does not influence progression of atherosclerosis in patients with familial hypercholesterolaemia. Eur J Clin Invest. 2004;34:94–9. doi:10.1111/j.1365-2362.2004.01303.x.PubMed

78.

Norata GD, Garlaschelli K, Ongari M, Raselli S, Grigore L, Benvenuto F, et al. Effect of the Toll-like receptor 4 (TLR-4) variants on intima–media thickness and monocyte-derived macrophage response to LPS. J Intern Med. 2005;258:21–7. doi:10.1111/j.1365-2796.2005.01509.x.PubMed

79.

Labrum R, Bevan S, Sitzer M, Lorenz M, Markus HS. Toll receptor polymorphisms and carotid artery intima–media thickness. Stroke. 2007;38:1179–84. doi:10.1161/01.STR.0000260184.85257.2b.PubMed

80.

Hernesniemi JA, Raitakari OT, Kähönen M, Juonala M, Hutri-Kähönen N, Marniemi J, et al. Toll-like receptor 4 gene (Asp299Gly) polymorphism associates with carotid artery elasticity. The cardiovascular risk in young Finns study. Atherosclerosis. 2008;198:152–9. doi:10.1016/j.atherosclerosis.2007.09.024.PubMed

81.

Ameziane N, Beillat T, Verpillat P, Chollet-Martin S, Aumont MC, Seknadji P, et al. Association of the Toll-like receptor 4 gene Asp299Gly polymorphism with acute coronary events. Arterioscler Thromb Vasc Biol. 2003;23:e61–4. doi:10.1161/01.ATV.0000101191.92392.1D.PubMed

82.

Boekholdt SM, Agema WR, Peters RJ, Zwinderman AH, van der Wall EE, et al. REgression GRowth Evaluation Statin Study Group. Variants of toll-like receptor 4 modify the efficacy of statin therapy and the risk of cardiovascular events. Circulation. 2003;107:2416–21. doi:10.1161/01.CIR.0000068311.40161.28.PubMed

83.

Yang IA, Holloway JW, Ye S. Southampton Atherosclerosis Study (SAS) Group. TLR4 Asp299Gly polymorphism is not associated with coronary artery stenosis. Atherosclerosis. 2003;170:187–90. doi:10.1016/S0021-9150(03)00286-7.PubMed

84.

Edfeldt K, Bennet AM, Eriksson P, Frostegård J, Wiman B, Hamsten A, et al. Association of hypo-responsive toll-like receptor 4 variants with risk of myocardial infarction. Eur Heart J. 2004;25:1447–53. doi:10.1016/j.ehj.2004.05.004.PubMed

85.

Morange PE, Tiret L, Saut N, Luc G, Arveiler D, Ferrieres J, et al. PRIME Study Group. TLR4/Asp299Gly, CD14/C-260T, plasma levels of the soluble receptor CD14 and therisk of coronary heart disease: the PRIME study. Eur J Hum Genet. 2004;12:1041–9. doi:10.1038/sj.ejhg.5201277.PubMed

86.

Holloway JW, Yang IA, Ye S. Variation in the toll-like receptor 4 gene and susceptibility to myocardial infarction. Pharmacogenet Genomics. 2005;15:15–21. doi:10.1097/01213011-200501000-00003.PubMed

87.

Zee RY, Hegener HH, Gould J, Ridker PM. Toll-like receptor 4 Asp299Gly gene polymorphism and risk of atherothrombosis. Stroke. 2005;36:154–7. doi:10.1161/01.STR.0000149948.31879.f0.PubMed

88.

Koch W, Hoppmann P, Pfeufer A, Schömig A, Kastrati A. Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population. Eur Heart J. 2006;27:2524–9. doi:10.1093/eurheartj/ehl231.PubMed

89.

Terry DF, Wilcox M, McCormick MA, Lawler E, Perls TT. Cardiovascular advantages among the offspring of centenarians. J Gerontol A Biol Sci Med Sci. 2003;58:M425–31.PubMed

90.

Terry DF, Wilcox MA, McCormick MA, Pennington JY, Schoenhofen EA, Andersen SL, et al. Lower all-cause, cardiovascular, and cancer mortality in centenarians' offspring. Am Geriatr Soc. 2004;52:2074–6. doi:10.1111/j.1532-5415.2004.52561.x.

91.

Lio D, Candore G, Crivello A, Scola L, Colonna-Romano G, Cavallone L, et al. Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease. J Med Genet. 2004;41:790–4. doi:10.1136/jmg.2004.019885.PubMed

92.

Grimaldi MP, Candore G, Vasto S, Caruso M, Caimi G, Hoffmann E, et al. Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population. J Leukoc Biol. 2006;79:611–5. doi:10.1189/jlb.0705416.PubMed

93.

Listì F, Candore G, Balistreri CR, Caruso M, Incalcaterra E, Hoffmann E, et al. Connexin37 1019 gene polymorphism in myocardial infarction patients and centenarians. Atherosclerosis. 2007;191:460–1. doi:10.1016/j.atherosclerosis.2006.08.009.PubMed

94.

Listì F, Candore G, Grimaldi MP, Lio D, Colonna-Romano G, Orlando V, et al. Alpha1-antitrypsin heterozygosity plays a positive role in attainment of longevity. Biogerontology. 2007;8:139–45. doi:10.1007/s10522-006-9041-y.PubMed

95.

Nuzzo D, Vasto S, Balistreri CR, Di-Carlo D, Listì F, Caimi G, et al. Role of proinflammatory alleles in longevity and atherosclerosis: results of studies performed on -1562C/T MMP-9 in centenarians and myocardial infarction patients from Sicily. Ann N Y Acad Sci. 2006;1089:496–501. doi:10.1196/annals.1386.048.PubMed

96.

Listì F, Caruso C, Balistreri CR, Grimaldi MP, Caruso M, Caimi G, et al. PECAM-1/CD31 in infarction and longevity. Ann N Y Acad Sci. 2007;1100:132–9. doi:10.1196/annals.1395.011.PubMed

97.

Balistreri CR, Candore G, Caruso M, Incalcaterra E, Franceschi C, Caruso C. Role of polymorphisms of CC-chemokine receptor-5 gene in acute myocardial infarction and biological implications for longevity. Haematologica. 2008;93:637–8. doi:10.3324/haematol.12239.PubMed

98.

Listì F, Caruso M, Incalcaterra E, Hoffmann E, Caimi G, Balistreri CR, et al. Pro-inflammatory gene variants in myocardial infarction and longevity: implications for pharmacogenomics. Curr Pharm Des. 2008;14:2678–85. doi:10.2174/138161208786264115.PubMed

99.

Balistreri CR, Candore G, Colonna-Romano G, Lio D, Caruso M, Hoffmann E, et al. Role of Toll-like receptor 4 in acute myocardial infarction and longevity. JAMA. 2004;292:2339–40. doi:10.1001/jama.292.19.2339.PubMed

100.

Nebel A, Flachsbart F, Schäfer A, Nothnagel M, Nikolaus S, Mokhtari NE, et al. Role of the toll-like receptor 4 polymorphism Asp299Gly in longevity and myocardial infarction in German men. Mech Ageing Dev. 2007;128:409–11. doi:10.1016/j.mad.2007.04.001.PubMed

101.

Barzi F, Woodward M, Marfisi RM, Tavazzi L, Valagussa F, Marchioli R. GISSI-Prevenzione Investigators. Mediterranean diet and all-causes mortality after myocardial infarction: results from the GISSI-Prevenzione trial. Eur J Clin Nutr. 2003;57:604–11. doi:10.1038/sj.ejcn.1601575.PubMed

102.

Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi C, et al. Caruso C. Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing. 2005;2:8. doi:10.1186/1742-4933-2-8.PubMed

103.

Schroder NW, Schumann RR. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis. 2005;5:156–64. doi:10.1016/S1473-3099(05)01308-3.PubMed

Title: TLR4 Polymorphisms and Ageing: Implications for the Pathophysiology of Age-Related Diseases
Authors: Carmela Rita Balistreri
Giuseppina Colonna-Romano
Domenico Lio
Giuseppina Candore
Calogero Caruso
Publication date: 01-07-2009
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 4/2009
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-009-9297-5

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Discussion

Please log in to get access to this content

Other articles of this Issue 4/2009

Abatacept Does Not Induce Direct Gene Expression Changes in Antigen-Presenting Cells

A Randomized Controlled Trial of Oral Administration of Tetanus Toxoid (TT) Versus Tetanus and Reduced Diphtheria (Td) in Pregnant Women

Imbalances Between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD

CD3ζ Expression and T Cell Proliferation are Inhibited by TGF-β1 and IL-10 in Cervical Cancer Patients

Enhanced Expression of Transcription Factor GATA-4 in Inflammatory Bowel Disease and Its Possible Regulation by TGF-β1

The Quality of Life of Children and Adolescents with X-Linked Agammaglobulinemia

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials