Metabolic endotoxemia: A novel concept in chronic disease pathology

Journal of Medical Sciences

Volumn 31, Issue 5, 2011, Pages 191-209

  Chang, Samantha ^a   Li, Liwu ^a  

^a VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY   (United States)

Author keywords

Chronic inflammatory diseases; Innate immunity signaling; Low grade endotoxemia

Indexed keywords

BACTERIUM LIPOPOLYSACCHARIDE; CELL NUCLEUS RECEPTOR; ENDOTOXIN; IMMUNOGLOBULIN G; LIVER X RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; RETINOID X RECEPTOR; TOLL LIKE RECEPTOR 4;

AGING; ALCOHOL CONSUMPTION; ALCOHOLISM; ARTICLE; ATHEROSCLEROSIS; CAUSAL ATTRIBUTION; ENDOTOXEMIA; ENDOTOXIN DETECTION; HUMAN; INFLAMMATION; INSULIN RESISTANCE; LIPID DIET; METABOLIC ENDOTOXEMIA; METASTASIS; MICROFLORA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PARKINSON DISEASE; PATHOGENESIS; PERIODONTAL DISEASE; PERIODONTITIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; SMOKING;

EID: 80055032775     PISSN: 10114564     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (132)

1. Sapkota AR, Berger S, Vogel TM. Human pathogens abundant in the bacterial metagenome of cigarettes. Environ Health Perspect. 2010;118:351-356.
2. Hasday JD, Bascon R, Costa JJ, Fitzgerald T, Dubin W. Bacterial endotoxin is an active component of cigarette smoke. Chest. 1999;115:829-835.
3. Sebastian A, Pehrson C, Larsson L. Elevated concentrations of endotoxin in indoor air due to cigarette smoking. J Environ Monit. 2006;8:519-522.
4. Larsson L, Szponar B, Pehrson C. Tobacco smoking increases dramatically air concentrations of endotoxin. Indoor Air. 2004;14:421-424.
5. Wiedermann CJ, Kiechl S, Dunzendorfer S, Schratzberger P, Egger G, Oberhollenzer F, Willeit J. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J Am Coll Cardiol. 1999;34:1975-1981.
6. Doyle I, Ratcliffe M, Walding A, Vanden Bon E, Dymond M, Tomlinson W, Tilley D, Shelton P, Dougall I. Differential gene expression analysis in human monocyte-derived macrophages: impact of cigarette smoke on host defence. Mol Immunol. 2010;47:1058-1065.
7. Valenca SS, Silva Bezerra F, Lopes AA, Romana-Souza B, Marinho Cavalcante MC, Lima AB, Gonzalves Koatz VL, Porto LC. Oxidative stress in mouse plasma and lungs induced by cigarette smoke and lipopolysaccharide. Environ Res. 2008;108:199-204.
8. Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflammaging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244-254.
9. Hajishengallis G. Too Old to Fight? Aging and its Toll on Innate Immunity. Mol Oral Microbiol. 2010;25:25-37.
10. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol. 2004;39:687-699.
11. Stout RD, Suttles J. Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age-associated microenvironmental changes. Immunol Rev. 2005;205:60-71.
12. Bode C, Bode JC. Effect of alcohol consumption on the gut. Best Pract Res Clin Gastroentrol. 2003;17:575-592.
13. Bode C, Bode JC. Activation of the innate immune system and alcoholic liver disease: effects of ethanol per se or enhanced intestinal translocation of bacterial toxins induced by ethanol? Alcohol Clin Exp Res. 2005;29(Suppl):166S-171S.
14. Wheeler MD. Endotoxin and Kupffer cell activation in alcoholic liver disease. Alcohol Res Health. 2003;27:300-306.
15. Bode C, Schäfer C, Bode JC. The role of gut-derived bacterial toxins (endotoxin) for the development of alcoholic liver disease in man. In: H.E Blum, C Bode, J.C Bode and R.B Sartor, Editors, Gut and the Liver, Kluwer, Dordrecht 1998, pp. 281-298 Falk Symposium 100.
16. Parlesak A, Schäfer C, Schütz T, Bode JC,Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. Journal of Hepatology 2000;23:742-747.
17. Fukui H, Brauner B, Bode JC, Bode C. Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: re-evaluation with an improved chromogenic assay, Journal of Hepatology 1991;12:162-169.
18. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761-1772.
19. Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374-2383.
20. Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev. 2010;31:817-844.
21. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137:1716-1724.
22. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Science Translational Medicine. 2009;1:6-14.
23. Laugerette F, Vors C, Peretti N, Michalski MC. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation. Biochimie. 2011;93:39-45.
24. Nicu EA, Laine ML, Morre SA, Van der Velden U, Loos BG. Soluble CD14 in periodontitis. Innate Immunity. 2009;15:121-128.
25. Pussinen PJ, Paju S, Mäntylä P, Sorsa T. Serum Microbial- and Host-Derived Markers of Periodontal Diseases: A Review. Curr Med Chem. 2007;14:2402-2412.
26. Grossi SG, Genco RJ. Periodontal disease and diabetes mellitus: a two-way relationship. Ann Periodontol. 1998;3:51-61.
27. Heimdahl A, Hall G, Hedberg M, Sandberg H, Söder PO, Tunér K, Nord CE. Detection and quantification by lysis-filtration of bacteremia after different oral surgical procedures. J Clin Microbiol. 1990;28:2205-2209.
28. Pussinen PJ, Tuomisto K, Jousilahti P, Havulinna AS, Sundvall J, Salomaa V. Endotoxemia, immune response to periodontal pathogens, and systemic inflammation associate with incident cardiovascular disease events. Arterioscler Thromb Vasc Biol. 2007;27:1433-1439.
29. Geerts SO, Nys M, De MP, Charpentier J, Albert A, Legrand V, Rompen EH. Systemic release of endotoxins induced by gentle mastication: association with periodontitis severity. J Periodontol. 2002;73:73-78.
30. Pussinen PJ, Vilkuna-Rautiainen T, Alfthan G, Palosuo T, Jauhiainen M, Sundvall J, Vesanen M, Mattila K, Asikainen S. Severe periodontitis enhances macrophage activation via increased serum lipopolysaccharide. Arterioscler Thromb Vasc Biol. 2004;24:2174-2180.
31. Peterson EM, Tontonoz P, Shah PK, Arditi M. TLR/ MyD88 and liver X receptor alpha signaling pathways reciprocally control Chlamydia pneumoniaeinduced acceleration of atherosclerosis. J Immunol. 2008;181:7176-7185.
32. Elisa Kallio KA, Buhlin K, Jauhiainen M, Keva R, Tuomainen AM, Klinge B, Gustafsson A, Pussinen PJ. Lipopolysaccharide associates with pro-atherogenic lipoproteins in periodontitis patients. Innate Immunity, 2008;14:247-253.
33. Stoll LL, Denning GM, Weintraub NL. Potential role of endotoxin as a proinflammatory mediator of atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24:2227-2236.
34. Perera PY, Vogel SN, Detore GR, Haziot A, Goyert SM. CD14-dependent and CD14-independent signaling pathways in murine macrophages from normal and CD14 knockout mice stimulated with lipopolysaccharide or taxol. J Immunol. 1997;158:4422-4429.
35. Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll like receptor 4. J Exp Med. 1999:189:1777-1782.
36. Medvedev AE, Piao W, Shoenfelt J, Rhee SH, Chen H, Basu S, Wahl LM, Fenton MJ, Vogel SN. Role of TLR4 tyrosine phosphorylation in signal transduction and endotoxin tolerance. J Biol Chem. 2007;282:16042-16053.
37. McGettrick AF, O'Neill LA. Localisation and trafficking of Toll-like receptors: an important mode of regulation. Curr Opin Immunol. 2010;22:20-27.
38. Barton GM, Kagan JC. A cell biological view of Tolllike receptor function: regulation through compartmentalization. Nat Rev Immunol. 2009;9:535-542. Epub 2009 Jun 26.
39. Lu YC, Kim I, Lye E, Shen F, Suzuki N, Suzuki S, Gerondakis S, Akira S, Gaffen SL, Yeh WC, Ohashi PS. Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated induction of proinflammatory cytokines. J Immunol. 2009;182:7212-7221.
40. Bonizzi G, Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004;25:280-288.
41. Qin J, Jiang Z, Qian Y, Casanova JL, Li X. IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness. J Biol Chem. 2004;279:26748-26753.
42. Song KW, Talamas FX, Suttmann RT, Olson PS, Barnett JW, Lee SW, Thompson KD, Jin S, Hekmat-Nejad M, Cai TZ, Manning AM, Hill RJ, Wong BR. The kinase activities of interleukin-1 receptor associated kinase (IRAK)-1 and 4 are redundant in the control of inflammatory cytokine expression in human cells. Mol Immunol. 2009;46:1458-1466.
43. Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell Signal. 2001;13:85-94.
44. Hirotani T, Yamamoto M, Kumagai Y, Uematsu S, Kawase I, Takeuchi O, Akira S. Regulation of lipopolysaccharide-inducible genes by MyD88 and Toll/IL-1 domain containing adaptor inducing IFNbeta. Biochem Biophys Res Commun. 2005;328:383-392.
45. Miller YI, Viriyakosol S, Worrall DS, Boullier A, Butler S, Witztum JL. Toll-like receptor 4-dependent andindependent cytokine secretion induced by minimally oxidized low-density lipoprotein in macrophages. Arterioscler. Thromb. Vasc. Biol. 2005;25:1213-1219.
46. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 2006;116:3015-3025.
47. Nguyen MT, Favelyukis S, Nguyen AK, Reichart D, Scott PA, Jenn A, Liu-Bryan R, Glass CK, Neels JG, Olefsky JM. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J. Biol. Chem. 2007;282:35279-35292.
48. Glass CK, Saijo K. Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat Rev Immunol. 2010;10:365-376.
49. Bensinger SJ, Tontonoz P. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature. 2008;454:470-477.
50. Bugge A, Mandrup S. Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation. PPAR Res. 2010;2010 pii: 169506.
51. Hong C, Tontonoz P. Coordination of inflammation and metabolism by PPAR and LXR nuclear receptors. Curr Opin Genet Dev. 2008;18:461-467.
52. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature. 2000;405:421-424.
53. Yessoufou A, Atègbo JM, Attakpa E, Hichami A, Moutairou K, Dramane KL, Khan NA. Peroxisome proliferator-activated receptor-alpha modulates insulin gene transcription factors and inflammation in adipose tissues in mice. Mol Cell Biochem. 2009;323:101-111.
54. Alvarez-Guardia D, Palomer X, Coll T, Davidson MM, Chan TO, Feldman AM, Laguna JC, Vázquez- Carrera M. The p65 subunit of NF-kappaB binds to PGC-1alpha, linking inflammation and metabolic disturbances in cardiac cells. Cardiovasc Res. 2010;87:449-458.
55. Wang LH, Yang XY, Zhang X, Farrar WL. Inhibition of adhesive interaction between multiple myeloma and bone marrow stromal cells by PPARgamma cross talk with NF-kappaB and C/EBP. Blood. 2007;110:4373-4384.
56. Bushue N, Wan YJ. Retinoid pathway and cancer therapeutics. Adv Drug Deliv Rev. 2010;62:1285-1298.
57. Castrillo A, Joseph SB, Vaidya SA, Haberland M, Fogelman AM, Cheng G, Tontonoz P. Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol Cell. 2003;12:805-816.
58. Huang W, Ghisletti S, Perissi V, Rosenfeld MG, Glass CK. Transcriptional integration of TLR2 and TLR4 signaling at the NCoR derepression checkpoint. Mol Cell. 2009;35:48-57.
59. Ricote M, Glass CK. PPARs and molecular mechanisms of transrepression. Biochim Biophys Acta. 2007;1771:926-935.
60. Ogawa S, Lozach J, Benner C, Pascual G, Tangirala RK, Westin S, Hoffmann A, Subramaniam S, David M, Rosenfeld MG, Glass CK. Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell. 2005;122:707-721.
61. Ghisletti S, Huang W, Ogawa S, Pascual G, Lin ME, Willson TM, Rosenfeld MG, Glass CK. Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol Cell. 2007;25:57-70.
62. Necela BM, Su W, Thompson EA. Toll-like receptor 4 mediates cross-talk between peroxisome proliferatoractivated receptor gamma and nuclear factor-kappaB in macrophages. Immunology. 2008;125:344-358.
63. Saubermann LJ, Nakajima A, Wada K, Zhao S, Terauchi Y, Kadowaki T, Aburatani H, Matsuhashi N, Nagai R, Blumberg RS. Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute colitis. Inflamm Bowel Dis. 2002;8:330-339.
64. Han J, Ulevitch RJ. Limiting inflammatory responses during activation of innate immunity. Nat Immunol. 2005;6:1198-1205.
65. An G. A model of TLR4 signaling and tolerance using a qualitative, particle-event-based method: introduction of spatially configured stochastic reaction cham bers (SCSRC). Math Biosci. 2009;217:43-52.
66. Maitra U, Gan L, Chang S, Li L. Low-dose endotoxin induces inflammation by selectively removing nuclear receptors and activating CCAAT/enhancer-binding protein δ. J Immunol. 2011;186:4467-4473.
67. Wiesner P, Choi SH, Almazan F, Benner C, Huang W, Diehl CJ, Gonen A, Butler S, Witztum JL, Glass CK, Miller YI. Low doses of lipopolysaccharide and minimally oxidized low-density lipoprotein cooperatively activate macrophages via nuclear factor kappa B and activator protein-1: possible mechanism for acceleration of atherosclerosis by subclinical endotoxemia. Circ Res. 2010;107:56-65.
68. Blomkalns AL, Stoll LL, Shaheen W, Romig-Martin SA, Dickson EW, Weintraub NL, Denning GM. Low level bacterial endotoxin activates two distinct signaling pathways in human peripheral blood mononuclear cells. J Inflamm (Lond). 2011; 8:4.
69. Olefsky JM, Glass CK. Macrophages, inflammation and insulin resistance. Annu Rev Physiol. 2010;72:219-246.
70. Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature 2002;420:333-336
71. Solinas G, Karin M. JNK1 and IKKbeta: molecular links between obesity and metabolic dysfunction. FASEB J. 2010;24:2596-2611.
72. Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev. 2010;31:817-844.
73. Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes 2006;55:1537-1545
74. Wasserman F. Handbook of Physiology. Washington, DC: American Physiology Society; 1965.
75. Suganami T, Nishida J, Ogawa Y. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol. 2005;25:2062-2068.
76. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116:1793-1801.
77. Gastaldelli A, Miyazaki Y, Pettiti M, Matsuda M, Mahankali S, Santini E, DeFronzo RA, Ferrannini E. Metabolic effects of visceral fat accumulation in type 2 diabetes. J Clin Endocrinol Metab. 2002;87:5098-5103.
78. Kleinridders A, Schenten D, Könner AC, Belgardt BF, Mauer J, Okamura T, Wunderlich FT, Medzhitov R, Brüning JC. MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab. 2009;10:249-259.
79. Solinas G, Vilcu C, Neels JG, Bandyopadhyay GK, Luo JL, Naugler W, Grivennikov S, Wynshaw-Boris A, Scadeng M, Olefsky JM, Karin M. JNK1 in hematopoietically derived cells contributes to dietinduced inflammation and insulin resistance without affecting obesity. Cell Metab. 2007;6:386-397.
80. Vijayvargia R, Mann K, Weiss HR, Pownall HJ, Ruan H. JNK deficiency enhances fatty acid utilization and diverts glucose from oxidation to glycogen storage in cultured myotubes. Obesity (Silver Spring). 2010;18:1701-1709.
81. Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, Puigserver P. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J. 2007;26:1913-1923.
82. Tanti JF, Grémeaux T, van Obberghen E, Le Marchand-Brustel Y. Serine/threonine phosphorylation of insulin receptor substrate 1 modulates insulin receptor signaling. J Biol Chem. 1994;269:6051-6057.
83. Kaperonis EA, Liapis CD, Kakisis JD, Dimitroulis D, Papavassiliou VG. Inflammation and Atherosclerosis. Eur J Vasc Endovasc Surg. 2006;31:386-393.
84. Ghanim H, Abuaysheh S, Sia CL, Korzeniewski K, Chaudhuri A, Fernandez-Real JM, Dandona P. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a highfat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care. 2009;32:2281-2287.
85. Rice JB, Stoll LL, Li WG, Denning GM, Weydert J, Charipar E, Richenbacher WE, Miller FJ Jr, Weintraub NL. Low-level endotoxin induces potent inflammatory activation of human blood vessels: inhibition by statins. Arterioscler Thromb Vasc Biol. 2003;23:1576-1582.
86. Maitra U, Baglin Samantha M, Li L. Inflammatory signaling networks as targets for pharmacological intervention of chronic diseases. Curr. Sig. Trans. 2009;Ther.4:103-110.
87. Wiedermann CJ, Kiechl S, Dunzendorfer S, Schratzberger P, Egger G, Oberhollenzer F, Willeit J. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J Am Coll Cardiol. 1999;34:1975-1981.
88. Miller MA, McTernan PG, Harte AL, Silva NF, Strazzullo P, Alberti KG, Kumar S, Cappuccio FP. Ethnic and sex differences in circulating endotoxin levels: A novel marker of atherosclerotic and cardiovascular risk in a British multi-ethnic population. Atherosclerosis. 2009;203:494-502.
89. Stoll LL, Denning GM, Weintraub NL. Potential role of endotoxin as a proinflammatory mediator of atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24:2227-2236.
90. Curtiss LK, Tobias PS. Emerging role of Toll-like receptors in atherosclerosis. J Lipid Res. 2009;50 Suppl:S340-345.
91. Yin K, Liao DF, Tang CK. ATP-binding membrane cassette transporter A1 (ABCA1): A possible link between inflammation and reverse cholesterol transport. Mol Med. 2010;16:438-449.
92. Tang C, Liu Y, Kessler PS, Vaughan AM, Oram JF. The macrophage cholesterol exporter ABCA1 functions as an anti-inflammatory receptor. J Biol Chem. 2009;284:32336-32343.
93. Packard RR, Lichtman AH, Libby P. Innate and adaptive immunity in atherosclerosis. Semin Immunopathol. 2009;31:5-22.
94. Libby P, di Carli M, Weissleder R. The vascular biology of atherosclerosis and imaging targets. J Nucl Med. 2010;51 Suppl 1:33S-37S.
95. Dutta G, Zhang P, Liu B. The lipopolysaccharide Parkinson's disease animal model: mechanistic studies and drug discovery. Fundam Clin Pharmacol. 2008;22:453-464.
96. Walter S, Letiembre M, Liu Y, Heine H, Penke B, Hao W, Bode B, Manietta N, Walter J, Schulz-Schuffer W, Fassbender K. Role of the toll-like receptor 4 in neuroinfl ammation in Alzheimer's disease. Cell Physiol Biochem. 2007;20:947-956.
97. Liu M, Bing G. Lipopolysaccharide animal models for Parkinson's disease. Parkinsons Dis. 2011;2011:327089.
98. Gao HM, Zhou H, Zhang F, Wilson BC, Kam W, Hong JS. HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. J Neurosci. 2011;31:1081-1092.
99. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007;55:453-462.
100. Pan W, Kastin AJ, Daniel J, Yu C, Baryshnikova LM, von Bartheld CS. TNFalpha trafficking in cerebral vascular endothelial cells. J Neuroimmunol. 2007;185:47-56.
101. Pan W, Kastin AJ. TNFalpha transport across the blood-brain barrier is abolished in receptor knockout mice. Exp Neurol. 2002;174:193-200.
102. Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J Neurochem. 2002;81:1285-1297.
103. Qin L, He J, Hanes RN, Pluzarev O, Hong JS, Crews FT. Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment. J Neuroinflammation. 2008;5:10.
104. Kacimi R, Giffard RG, Yenari MA. Endotoxinactivated microglia injure brain derived endothelial cells via NF-κB, JAK-STAT and JNK stress kinase pathways. J Inflamm (Lond). 2011;8:7.
105. Leitinger N. The role of phospholipid oxidation products in inflammatory and autoimmune diseases: evidence from animal models and in humans. Subcell Biochem. 2008;49:325-350.
106. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860-867.
107. Huang B, Zhao J, Li H, He KL, Chen Y, Chen SH, Mayer L, Unkeless JC, Xiong H. Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 2005; 65:5009-5014.
108. El-Omar EM, Ng MT, Hold GL. Polymorphisms in Toll-like receptor genes and risk of cancer. Oncogene. 2008;27:244-252.
109. Apetoh L, Tesniere A, Ghiringhelli F, Kroemer G, Zitvogel L. Molecular interactions between dying tumor cells and the innate immune system determine the efficacy of conventional anticancer therapies. Cancer Res. 2008;68:4026-4030.
110. Lapteva N, Aldrich M, Rollins L, Ren W, Goltsova T, Chen SY, Huang XF. Attraction and activation of dendritic cells at the site of tumor elicits potent antitumor immunity. Mol Ther. 2009;17:1626-1636.
111. del Fresno C, Otero K, Gómez-García L, González-León MC, Soler-Ranger L, Fuentes-Prior P, Escoll P, Baos R, Caveda L, García F, Arnalich F, López-Collazo E. Tumor cells deactivate human monocytes by up-regulating IL-1 receptor associated kinase-M expression via CD44 and TLR4. J Immunol. 2005;174:3032-3040.
112. Hsu RY, Chan CH, Spicer JD, Rousseau MC, Giannias B, Rousseau S, Ferri LE. LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res. 2011;71:1989-1998.
113. Simiantonaki N, Kurzik-Dumke U, Karyofylli G, Jayasinghe C, Michel-Schmidt R, Kirkpatrick CJ. Reduced expression of TLR4 is associated with the metastatic status of human colorectal cancer. Int J Mol Med. 2007;20:21-29.
114. Sun Q, Liu Q, Zheng Y, Cao X. Rapamycin suppresses TLR4-triggered IL-6 and PGE(2) production of colon cancer cells by inhibiting TLR4 expression and NF-kappaB activation. Mol Immunol. 2008;45:2929-2936.
115. González-Reyes S, Marín L, González L, González LO, del Casar JM, Lamelas ML, González-Quintana JM, Vizoso FJ. Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer. 2010;10:665.
116. Thuringer D, Hammann A, Benikhlef N, Fourmaux E, Bouchot A, Wettstein G, Solary E, Garrido C. Transactivation of the epidermal growth factor receptor by heat shock protein 90 via Toll-like receptor 4 contributes to the migration of glioblastoma cells. J Biol Chem. 2011;286:3418-3428.
117. Park HD, Lee Y, Oh YK, Jung JG, Park YW, Myung K, Kim KH, Koh SS, Lim DS. Pancreatic adenocarcinoma upregulated factor promotes metastasis by regulating TLR/CXCR4 activation. Oncogene. 2011;30:201-211.
118. Zhang JJ, Wu HS, Wang L, Tian Y, Zhang JH, Wu HL. Expression and significance of TLR4 and HIF- 1alpha in pancreatic ductal adenocarcinoma. World J Gastroenterol. 2010;16:2881-2888.
119. Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol. 2008;10:1349-1355.
120. Zhang YB, He FL, Fang M, Hua TF, Hu BD, Zhang ZH, Cao Q, Liu RY. Increased expression of Tolllike receptors 4 and 9 in human lung cancer. Mol Biol Rep. 2009;36:1475-1481.
121. Voelcker V, Gebhardt C, Averbeck M, Saalbach A, Wolf V, Weih F, Sleeman J, Anderegg U, Simon J. Hyaluronan fragments induce cytokine and metalloprotease upregulation in human melanoma cells in part by signalling via TLR4. Exp Dermatol. 2008;17:100-107.
122. Al-Aly Z, Pan H, Zeringue A, Xian H, McDonald JR, El-Achkar TM, Eisen S. Tumor necrosis factor-α blockade, cardiovascular outcomes, and survival in rheumatoid arthritis. Transl Res. 2011;157:10-18.
123. Duan SZ, Usher MG, Mortensen RM. PPARs: the vasculature, inflammation and hypertension. Curr Opin Nephrol Hypertens. 2009;18:128-133.
124. Naiki Y, Sorrentino R, Wong MH, Michelsen KS, Shimada K, Chen S, Yilmaz A, Slepenkin A, Schröder NW, Crother TR, Bulut Y, Doherty TM, Bradley M, Shaposhnik Z, Peterson EM, Tontonoz P, Shah PK, Arditi M. TLR/MyD88 and liver X receptor alpha signaling pathways reciprocally control Chlamydia pneumonia-induced acceleration of atherosclerosis. J Immunol. 2008;181:7176-7185.
125. Haas B, Leonard F, Ernens I, Rodius S, Vausort M, Rolland-Turner M, Devaux Y, Wagner DR. Adenosine Reduces Cell Surface Expression of Toll-Like Receptor 4 and Inflammation in Response to Lipopolysaccharide and Matrix Products. J Cardiovasc Transl Res. 2011 May 3 [Epub ahead of print].
126. Pussinen PJ, Havulinna AS, Lehto M, Sundvall J, Salomaa V. Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care. 2011;34:392-397.
127. Gettrick AF, O'Neill LAJ. Localisation and traffic cking of Toll-like receptors: an important mode of regulation. Curr Op Immunol, 2010;22:20-27.
128. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003;301:640-643.
129. Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S, Miyake K. Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Biochem Biophys Res Commun. 2008;368:94-99.
130. Nakarai H, Yamashita A, Nagayasu S, Iwashita M, Kumamoto S, Ohyama H, Hata M, Soga Y, Kushiyama A, Asano T, Abiko Y, Nishimura F. Adipocytemacrophage interaction may mediate LPS-induced low-grade inflammation: potential link with metabolic complications. Innate Immun. 2011 Jan 14 [Epub ahead of print].
131. O'Neill LA, Bryant CE, Doyle SL. Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev. 2009;61:177-197.
132. Gallagher EJ, LeRoith D, Karnieli E. Insulin resistance in obesity as the underlying cause for metabolic syndrome. Mt Sinai J Med. 2010;77:511-523.