Toll-like receptors and diabetes: A therapeutic perspective

Clinical Science

Volumn 122, Issue 5, 2012, Pages 203-214

  Dasu, Mohan R ^a   Ramirez, Sandra ^a   Isseroff, Roslyn R ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Hyperglycaemia; Inflammation; Insulin resistance; Oxidative stress; Toll like receptor; Type 2 diabetes

Indexed keywords

AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; BENFOTIAMINE; CANDESARTAN; CAPSAICIN; CINNAMALDEHYDE; CURCUMIN; CYTOKINE; DOCOSAHEXAENOIC ACID; EPIGALLOCATECHIN GALLATE; FATTY ACID; GINGER EXTRACT; HELENALIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IBUDILAST; ICOSAPENTAENOIC ACID; LUTEOLIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; OPN 305; OPN 401; PIOGLITAZONE; POLLINEX QUATRO; REACTIVE OXYGEN METABOLITE; TOLL LIKE RECEPTOR; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; DIABETES MELLITUS; DIABETIC NEPHROPATHY; EXPERIMENTAL ANIMAL; GLUCOSE BLOOD LEVEL; HUMAN; IMMUNE RESPONSE; INFLAMMATION; MOLECULAR MECHANICS; NONHUMAN; PATHOGENESIS; PREVALENCE; PRIORITY JOURNAL; REVIEW; SYSTEMATIC REVIEW; HYPERGLYCEMIA; IMMUNOLOGY; INNATE IMMUNITY; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

BLOOD GLUCOSE; CYTOKINES; DIABETES COMPLICATIONS; DIABETES MELLITUS; FATTY ACIDS, NONESTERIFIED; HUMANS; HYPERGLYCEMIA; IMMUNITY, INNATE; INFLAMMATION; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 84855481978     PISSN: 01435221     EISSN: None     Source Type: Journal    
DOI: 10.1042/CS20110357     Document Type: Review

References (148)

1. Centers for Disease Control and Prevention (2011) National diabetes fact sheet: general information and national estimates on diabetes and prediabetes in the United States, U.S. Department of Health and Human Services, Atlanta, GA (http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf)
2. Danaei, G., Finucane, M. M., Lu, Y., Singh, G. M., Cowan, M. J., Paciorek, C. J., Lin, J. K., Farzadfar, F., Khang, Y. H., Stevens, G. A. et al. (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378, 31-40
3. Narayan, K. M., Boyle, J. P., Thompson, T. J., Sorensen, S. W. and Williamson, D. F. (2003) Lifetime risk for diabetes mellitus in the United States. JAMA, J. Am. Med. Assoc. 290, 1884-1890
4. Brownlee, M. (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54, 1615-1625
5. DeFronzo, R. A. and Ferrannini, E. (1991) Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14, 173-194
6. Hofmann, M. A., Schiekofer, S., Isermann, B., Kanitz, M., Henkels, M., Joswig, M., Treusch, A., Morcos, M., Weiss, T., Borcea, V. et al. (1999) Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-κB. Diabetologia 42, 222-232
7. Olefsky, J. M. and Glass, C. K. (2010) Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 72, 219-246
8. Pickup, J. C. and Crook, M. A. (1998) Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 41, 1241-1248
9. Pino, S. C., Kruger, A. J. and Bortell, R. (2010) The role of innate immune pathways in type 1 diabetes pathogenesis. Curr. Opin. Endocrinol. Diabetes Obes. 17, 126-130
10. Zipris, D. (2010) Toll-like receptors and type 1 diabetes. Adv. Exp. Med. Biol. 654, 585-610
11. Wong, F. S. and Wen, L. (2008) Toll-like receptors and diabetes. Ann. N.Y. Acad. Sci. 1150, 123-132
12. Takeda, K., Kaisho, T. and Akira, S. (2003) Toll-like receptors. Annu. Rev. Immunol. 21, 335-376
13. Uematsu, S. and Akira, S. (2006) Toll-like receptors and innate immunity. J. Mol. Med. 84, 712-725
14. Kawai, T. and Akira, S. (2006) TLR signaling. Cell Death Differ. 13, 8156-8825
15. Wagner, H. (2006) Endogenous TLR ligands and autoimmunity. Adv. Immunol. 91, 159-173
16. Tsan, M. F. and Gao, B. (2004) Endogenous ligands of Toll-like receptors. J. Leukocyte Biol. 76, 514-519
17. Taylor, K. R., Trowbridge, J. M., Rudisill, J. A., Termeer, C. C., Simon, J. C. and Gallo, R. L. (2004) Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J. Biol. Chem. 279, 17079-17084
18. Osterloh, A. and Breloer, M. (2008) Heat shock proteins: linking danger and pathogen recognition. Med. Microbiol. Immunol. 197, 1-8
19. Chiu, Y. C., Lin, C. Y., Chen, C. P., Huang, K. C., Tong, K.M., Tzeng, C. Y., Lee, T. S., Hsu, H. C. and Tang, C. H. (2009) Peptidoglycan enhances IL-6 production in human synovial fibroblasts via TLR2 receptor, focal adhesion kinase, Akt, and AP-1- dependent pathway. J. Immunol. 183, 2785-2792
20. Hreggvidsdottir, H. S., Ostberg, T., Wähämaa, H., Schierbeck, H., Aveberger, A. C., Klevenvall, L., Palmblad, K., Ottosson, L., Andersson, U. and Harris, H. E. (2009) The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation. J. Leukocyte Biol. 86, 655-662
21. Dasu, M. R., Devaraj, S., Park, S. and Jialal, I. (2010) Increased toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes Care 33, 861-868
22. Mohammad, M. K., Morran, M., Slotterbeck, B., Leaman, D. W., Sun, Y., Grafenstein, H., Hong, S. C. and McInerney, M. F. (2006) Dysregulated Toll-like receptor expression and signaling in bone marrow-derived macrophages at the onset of diabetes in the non-obese diabetic mouse. Int. Immunol. 18, 1101-1113
23. Kim, H. S., Han, M. S., Chung, K. W., Kim, S., Kim, E., Kim, M. J., Jang, E., Lee, H. A., Youn, J., Akira, S. and Lee, M. S. (2007) Toll-like receptor 2 senses β-cell death and contributes to the initiation of autoimmune diabetes. Immunity 27, 321-333
24. Reyna, S. M., Ghosh, S., Tantiwong, P., Meka, C. S., Eagan, P., Jenkinson, C. P., Cers osimo, E., Defronzo, R. A., Coletta, D. K., Sriwijitkamol, A. and Musi, N. (2008) Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes 57, 2595-2602
25. Creely, S. J., McTernan, P. G., Kusminski, C. M., Fisher, M., Da Silva, N. F., Khanolkar, M., Evans, M., Harte, A. L. and Kumar, S. (2007) Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 292, E740-E747
26. Song, M. J., Kim, K. H., Yoon, J. M. and Kim, J. B. (2006) Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. Biochem. Biophys. Res. Commun. 346, 739-745
27. Senn, J. J. (2006) Toll-like receptor-2 is essential for the development of palmitate-induced insulin resistance in myotubes. J. Biol. Chem. 281, 26865-26875
28. Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H. and Flier, J. S. (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015-3025
29. Dasu, M. R.,Devaraj, S., Zhao, L., Hwang, D. H. and Jialal, I. (2008) High glucose induces toll-like receptor expression in human monocytes: mechanism of activation. Diabetes 57, 3090-3098
30. Schwartz, E. A., Zhang, W. Y., Karnik, S. K., Borwege, S., Anand, V. R., Laine, P. S., Su, Y. and Reaven, P. D. (2010) Nutrient modification of the innate immune response: a novel mechanism by which saturated fatty acids greatly amplify monocyte inflammation. Arterioscler. Thromb. Vasc. Biol. 30, 802-808
31. Devaraj, S., Jialal, I., Yun, J. M. and Bremer, A. (2010) Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications. Metab. Clin. Exp. 60, 256-259
32. Eguchi, M., McMillan, M., Nguyen, C., Teo, J. L., Chi, E. Y., Henderson, Jr, W.R. and Kahn, M. (2003) Chemogenomics with peptide secondary structure mimetics. Comb. Chem. High-Throughput Screen. 6, 611-621
33. Schiekofer, S., Andrassy, M., Chen, J., Rudofsky, G., Schneider, J., Wendt, T., Stefan, N., Humpert, P., Fritsche, A., Stumvoll, M. et al. (2003) Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK and nuclear factor κB in PBMCs. Diabetes 52, 621-633
34. Yan, S. F., Ramasamy, R. and Schmidt, A. M. (2008) Mechanisms of disease: advanced glycation endproducts and their receptor in inflammation and diabetes complications. Nat. Clin. Pract. Endocrinol. Metab. 4, 285-293
35. Davis, J. E., Gabler, N. K., Walker-Daniels, J. and Spurlock, M. E. (2008) Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat. Obesity 16, 1248-1255
36. Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 329, 977-986
37. UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837-853
38. Shanmugam, N., Reddy, M. A., Guha, M. and Natarajan, R. (2003) High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells. Diabetes 52, 1256-1264
39. Koya, D. and King, G. L. (1998) Protein kinase C activation and the development of diabetic complications. Diabetes 47, 859-866
40. Chait, A. and Bornfeldt, K. E. (2009) Diabetes and atherosclerosis: is there a role for hyperglycemia? J. Lipid Res. 50 (Suppl.), S335-S339
41. Edfeldt, K., Swedenborg, J., Hansson, G. K. and Yan, Z. Q. (2002) Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 105, 1158-1161
42. Fan, J., Frey, R. S. and Malik, A. B. (2003) TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase. J. Clin. Invest. 112, 1234-1243
43. Yang, X., Coriolan, D., Murthy, V., Schultz, K., Golenbock, D. T. and Beasley, D. (2005) Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling. Am. J. Physiol. Heart Circ. Physiol. 289, H1069-H1076
44. Kaisho, S. and Akira, S. (2003) Regulation of dendritic cell function through Toll-like receptors. Curr. Mol. Med. 3, 373-385
45. Miller, L. S., Sorensen, O. E., Liu, P. T., Jalian, H. R., Eshtiaghpour, D., Behmanesh, B. E., Chung, W., Starner, T. D., Kim, J., Sieling, P. A. et al. (2005) TGF-α regulates TLR expression and function on epidermal keratinocytes. J. Immunol. 174, 6137-6143
46. Saillan-Barreau, C., Cousin, B., Andre, M., Villena, P., Casteilla, L. and Penicaud, L. (2003) Human adipose cells as candidates in defense and tissue remodeling phenomena. Biochem. Biophys. Res. Commun. 309, 502-505
47. B'es-Houtmann, S., Roche, R., Hoareau, L., Gonthier, M. P., Festy, F., Caillens, H., Gasque, P., Lefebvre d'Hellencourt, C. and Cesari, M. (2007) Presence of functional TLR2 and TLR4 on human adipocytes. Histochem. Cell Biol. 127, 131-137
48. Lee, J. Y., Zhao, L., Youn, H. S., Weatherill, A. R., Tapping, R., Feng, L., Lee, W. H., Fitzgerald, K. A. and Hwang, D. H (2004) Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J. Biol. Chem. 279, 16971-16979
49. Tripathy, D., Mohanty, P., Dhindsa, S., Syed, T., Ghanim, H., Aljada, A. and Dandona, P. (2003) Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes 52, 2882-2887
50. Lee, J. Y. and Hwang, D. H. (2006) The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors. Mol. Cells 30, 21, 174-185
51. Lee, J. Y., Plakidas, A., Lee,W. H., Heikkinen, A., Chanmugam, P., Bray, G. and Hwang, D. H. (2003) Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J. Lipid Res. 44, 479-486
52. Coll, T., Palomer, X., Blanco-Vaca, F., Escol'a-Gil, J. C., Sánchez, R. M., Laguna, J. C. and Vázquez-Carrera, M. (2010) Cyclooxygenase 2 inhibition exacerbates palmitate-induced inflammation and insulin resistance in skeletal muscle cells. Endocrinology 151, 537-548
53. Aas, V., Rokling-Andersen, M., Wensaas, A. J., Thoresen, G. H., Kase, E. T. and Rustan, A. C. (2005) Lipid metabolism in human skeletal muscle cells: effects of palmitate and chronic hyperglycemia. Acta Physiol. Scand. 183, 31-41
54. Ajuwon, K. M. and Spurlock, M. E. (2005) Palmitate activates the NF-κB transcription factor and induces IL-6 and TNFα expression in 3T3-L1 adipocytes. J. Nutr. 135, 1841-1846
55. Böni-Schnetzler, M., Boller, S., Debray, S., Bouzakri, K., Meier, D. T., Prazak, R., Kerr-Conte, J., Pattou, F., Ehses, J. A., Schuit, F. C. and Donath, M. Y. (2009) Free fatty acids induce a proinflammatory response in islets via the abundantly expressed interleukin-1 receptor I. Endocrinology 150, 5218-5229
56. Himes, R. W. and Smith, C. W. (2010) TLR2 is critical for diet-induced metabolic syndrome in a murine model. FASEB J. 24, 731-739
57. Ehses, J. A., Meier, D. T., Wueest, S., Rytka, J., Boller, S., Wielinga, P. Y., Schraenen, A., Lemaire, K., Debray, S., Van Lommel, L. et al. (2010) Toll-like receptor 2-deficient mice are protected from insulin resistance and β cell dysfunction induced by a high-fat diet. Diabetologia 53, 1795-1806
58. Kuo, L. H., Tsai, P. J., Jiang, M. J., Chuang, Y. L., Yu, L., Lai, K. T. and Tsai, Y. S. (2011) Toll-like receptor 2 deficiency improves insulin sensitivity and hepatic insulin signalling in the mouse. Diabetologia 54, 168-179
59. Vessby, B., Uusitupa, M., Hermansen, K., Riccardi, G., Rivellese, A. A., Tapsell, L. C., Nälsén, C., Berglund, L., Louheranta, A., Rasmussen, B. M. et al. (2001) KANWU Study. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU Study. Diabetologia 44, 312-319
60. Dasu, M. R. and Jialal, I. (2011) Free fatty acids in the presence of high glucose amplify monocyte inflammation via Toll-like receptors. Am. J. Physiol. Endocrinol. Metab. 300, E145-E154
61. Davis, J. E., Braucher, D. R., Walker-Daniels, J. and Spurlock, M. E. (2010) Absence of TLR2 protects against high-fat diet-induced inflammation and results in greater insulin-stimulated glucose transport in cultured adipocytes. J. Nutr. Biochem. 4, 28
62. Suganami, T., Mieda, T., Itoh, M., Shimoda, Y., Kamei, Y. and Ogawa, Y. (2007) Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation. Biochem. Biophys. Res. Commun. 354, 45-49
63. Poggi, M., Bastelica, D., Gual, P., Iglesias, M. A., Gremeaux, T., Knauf, C., Peiretti, F., Verdier, M., Juhan-Vague, I., Tanti, J. F., Burcelin, R. and Alessi, M. C. (2007) C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet. Diabetologia 50, 1267-1276
64. Tsukumo, D. M., Carvalho-Filho, M. A., Carvalheira, J. B., Prada, P. O., Hirabara, S. M., Schenka, A. A., Araújo, E. P., Vassallo, J., Curi, R., Velloso, L. A. and Saad, M. J. (2007) Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56, 1986-1998
65. Kim, F., Pham, M., Luttrell, I., Bannerman, D. D., Tupper, J., Thaler, J., Hawn, T. R., Raines, E. W. and Schwartz, M.W. (2008) Toll-like receptor-4 mediates vascular inflammation and insulin resistance in dietinduced obesity. Circ. Res. 100, 1589-1596
66. Nguyen, M. T., Favelyukis, S., Nguyen, A. K., Reichart, D., Scott, P. A., Jenn, A., Liu-Bryan, R., Glass, C. K., Neels, J. G. and Olefsky, J. M. (2007) 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. 282, 35279-35292
67. Wellen, K. E. and Hotamisligil, G. S. (2005) Inflammation, stress, and diabetes. J. Clin. Invest. 115, 1111-1119
68. Caricilli, A. M., Nascimento, P. H., Pauli, J. R., Tsukumo, D. M., Velloso, L. A. and Carvalheira, J. B. (2008) Inhibition of toll-like receptor 2 expression improves insulin sensitivity and signaling in muscle and white adipose tissue of mice fed a high-fat diet. J. Endocrinol. 199, 399-406
69. Deopurkar, R., Ghanim, H., Friedman, J., Abuaysheh, S., Sia, C. L., Mohanty, P., Viswanathan, P., Chaudhuri, A. and Dandona, P. (2010) Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling- 3. Diabetes Care 33, 991-997
70. Ghanim, H., Abuaysheh, S., Sia, C. L., Korzeniewski, K., Chaudhuri, A., Fernandez-Real, J. M. and Dandona, P. (2009) Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 32, 2281-2287
71. Mohanty, P., Hamouda,W., Garg, R., Aljada, A., Ghanim, H. and Dandona, P. (2000) Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J. Clin. Endocrinol Metab. 85, 2970-2973
72. Venugopal, S. K., Devaraj, S., Yang, T. and Jialal, I. (2002) α-Tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-α. Diabetes 51, 3049-3054
73. Kowluru, R. A. and Odenbach, S. (2004) Role of interleukin-1b in the pathogenesis of diabetic retinopathy. Br. J. Ophthalmol. 88, 1343-1347
74. Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H. P. et al. (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycemic damage. Nature 404, 787-790
75. Shashkin, P. N., Jain, N., Miller, Y. I., Rissing, B. A., Huo, Y., Keller, S. R., Vandenhoff, G. E., Nadler, J. L. and McIntyre, T. M. (2006) Insulin and glucose play a role in foam cell formation and function. Cardiovasc. Diabetol. 20, 5-13
76. Maedler, K., Sergeev, P., Ris, F., Oberholzer, J., Joller-Jemelka, H. I., Spinas, G. A., Kaiser, N., Halban, P. A. and Donath, M. Y. (2002) Glucose-induced β cell production of IL-1b contributes to glucotoxicity in human pancreatic islets. J. Clin. Invest. 110, 851-860
77. Asakawa, H., Miyagawa, J., Hanafusa, T., Kuwajima, M. and Matsuzawa, Y. (1997) High glucose and hyperosmolarity increase secretion of interleukin-1b in cultured human aortic endothelial cells. J. Diabetes Complications 11, 176-179
78. Trinchieri, G. and Sher, A. (2007) Cooperation of Toll-like receptor signals in innate immune defence. Nat. Rev. Immunol. 7, 179-190
79. Medzhitov, R. (2001) Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1, 135-145
80. Dasu, M. R., Thangappan, R.K., Bourgette, A., DiPietro, L. A., Isseroff, R. and Jialal, I. (2010) TLR2 expression and signaling-dependent inflammation impair would healing in diabetic mice. Lab. Invest. 90, 1628-1636
81. Kadri-Hassani, N., Leger, C. L. and Descomps, B. (1995) The fatty acid bimodal action on superoxide production by human adherent monocytes under phorbol 12-myristate 13-acetate or diacylglycerol activation can be explained by the modulation of protein kinase C and p47phox translocation. J. Biol. Chem. 270, 15111-15118
82. Dasu, M. R., Devaraj, S. and Jialal, I. (2007) High glucose induces IL-1β expression in human monocytes: mechanistic insights. Am. J. Physiol. Endocrinol. Metab. 293, E337-E346
83. Asehnoune, K., Strassheim, D., Mitra, S., Yeol Kim, J. and Abraham, E. (2005) Involvement of PKCα/β in TLR4 and TLR2 dependent activation of NF-κB. Cell. Signalling 17, 385-394
84. Thallas-Bonke, V., Thorpe, S. R., Coughlan, M. T., Fukami, K., Yap, F. Y., Sourris, K. C., Penfold, S. A., Bach, L. A., Cooper, M. E. and Forbes, J. M. (2008) Inhibition of NADPH oxidase prevents advanced glycation end product-mediated damage in diabetic nephropathy through a protein kinase C-α-dependent pathway. Diabetes 57, 460-469
85. Qi, X., Vallentin, A., Churchill, E. and Mochly-Rosen, D. (2007) δPKC participates in the endoplasmic reticulum stress-induced response in cultured cardiac myocytes and ischemic heart. J. Mol. Cell Cardiol. 43, 420-428
86. Bey, E. A., Xu, B., Bhattacharjee, A., Oldfield, C. M., Zhao, X., Li, Q., Subbulakshmi, V., Feldman, G. M., Wientjes, F. B. and Cathcart, M.K (2004) Protein kinase Cδ is required for p47Phox phosphorylation and translocation in activated human monocytes. J. Immunol. 173, 5730-5738
87. Ryan, K. A., Smith, M.F. Jr., Sanders, M. K. and Ernst, P. B. (2004) Reactive oxygen and nitrogen species differentially regulate Toll-like receptor 4-mediated activation of NF-κB and interleukin-8 expression. Infect. Immun. 72, 2123-2130
88. Giacco, F. and Brownlee, M. (2010) Oxidative stress and diabetic complications. Circ. Res. 107, 1058-1070
89. Babior, B.M (1999) NADPH oxidase: an update. Blood 93, 1464-1476
90. Gill, R., Tsung, A. and Billiar, T. (2010) Linking oxidative stress to inflammation: Toll-like receptors. Free Radical Biol. Med. 48, 1121-1132
91. Xiang, M., Fan, J. and Fan, J. (2010) Association of Toll-like receptor signaling and reactive oxygen species: a potential therapeutic target for posttrauma acute lung injury. Mediators Inflamm. 2010, 916425
92. Nakamura, S., Takamura, T., Matsuzawa-Nagata, N., Takayama, H., Misu, H., Noda, H., Nabemoto, S., Kurita, S., Ota, T., Ando, H. et al. (2009) Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J. Biol. Chem. 284, 14809-14818
93. Maloney, E., Sweet, I. R., Hockenbery, D. M., Pham, M., Rizzo, N. O., Tateya, S., Handa, P., Schwartz, M.W. and Kim, F. (2009) Activation of NF-κB by palmitate in endothelial cells: a key role for NADPH oxidase-derived superoxide in response to TLR4 activation. Arterioscler Thromb Vasc Biol. 29, 1370-1375
94. Devaraj, S., Dasu, M. R. and Jialal, I. (2010) Diabetes is a proinflammatory state: a translational perspective. Expert Rev. Endocrinol. Metab. 5, 19-28
95. O'Neill, L. A. (2003) Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases. Curr. Opin. Pharmacol. 3, 396-403
96. Keogh, B. and Parker, A. E. (2011) Toll-like receptors as targets for immune disorders. Trends Pharmacol. Sci. 32, 435-442
97. Dunne, A., Marshall, N. A. and Mills, H.G.K. (2011) TLR based therapeutics. Curr. Opin. Pharmacol. 11, 1-8
98. Hennessy, E. J., Parker, A. E. and O'Neill, A. J. (2010) Targeting Toll-like receptors: emerging therapeutics? Nat. Rev. Drug Discovery 9, 293-307
99. Ortego, M., Bustos, C., Hernandez-Presa, M. A., Tunon, J., Diaz, C., Hernandez, G. and Egido, J. (1999) Atorvastatin reduces NF-κB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis 147, 253-261
100. Zelvyte, I., Dominaitiene, R., Crisby, M. and Janciauskiene, S. (2002) Modulation of inflammatory mediators and PPARγ and NFκB expression by pravastatin in response to lipoproteins in human monocytes in vitro. Pharmacol. Res. 45, 147-154
101. Weis, M., Pehlivanli, S., Meiser, B. M. and von Scheidt, W. (2001) Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation. J. Am. Coll. Cardiol. 38, 814-818
102. Zeuke, S., Ulmer, A. J., Kusumoto, S., Katus, H. A. and Heine, H. (2002) TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS. Cardiovasc. Res. 56, 126-134
103. + monocytes. Arterioscler. Thromb. Vasc. Biol. 25, 1439-1445
104. Stoll, L. L., Denning, G. M. and Weintraub, N. L. (2006) Endotoxin, TLR4 signaling and vascular inflammation: potential therapeutic targets in cardiovascular disease. Curr. Pharm. Des. 12, 4229-4245
105. Niessner, A., Steiner, S., Speidl,W. S., Pleiner, J., Seidinger, D., Maurer, G., Goronzy, J. J., Weyand, C. M., Kopp, C. W., Huber, K. et al. (2006) Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo. Atherosclerosis 189, 408-413
106. Neurauter, G., Wirleitner, B., Laich, A., Schennach, H., Weiss, G. and Fuchs, D. (2003) Atorvastatin suppresses interferon-γ -induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Clin. Exp. Immunol. 131, 264-267
107. Rice, J. B., Stoll, L. L., Li,W. G., Denning, G. M., Weydert, J., Charipar, E., Richenbacher, W. E., Miller, Jr, F.J. and Weintraub, N. L. (2003) Low-level endotoxin induces potent inflammatory activation of human blood vessels: inhibition by statins. Arterioscler. Thromb. Vasc. Biol. 23, 1576-1582
108. Garber, A. J. (1998) Vascular disease and lipids in diabetes. Med. Clin. North Am. 82, 931-948
109. European Diabetes Policy Group (1999) A desktop guide to type 2 diabetes mellitus. Diabetic Med. 16, 716-730
110. Daynes, R. A. and Jones, D. C. (2002) Emerging roles of PPARs in inflammation and immunity. Nat. Rev. Immunol. 2, 748-759
111. Dehmer, T., Heneka, MT., Sastre, M., Dichgans, J. and Schulz, J. B. (2004) Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with IκBα induction and block of NFκB and iNOS activation. J. Neurochem. 88, 494-501
112. Tao, L., Liu, H. R., Gao, E., Teng, Z. P., Lopez, B. L., Christopher, T. A., Ma, X. L., Batinic-Haberle, I., Willette, R. N., Ohlstein, E. H. and Yue, T. L. (2003) Antioxidative, antinitrative, and vasculoprotective effects of a peroxisome proliferator-activated receptor-γ agonist in hypercholesterolemia. Circulation 108, 2805-2811
113. Dasu, M. R., Park, S., Devaraj, S. and Jialal, I. (2009) Pioglitazone inhibits Toll-like receptor expression and activity in human monocytes and db/db mice. Endocrinology 150, 3457-3464
114. Ramirez, S. H., Heilman, D., Morsey, B., Potula, R., Haorah, J. and Persidsky, Y. (2008) Activation of peroxisome proliferator-activated receptor γ (PPARγ) suppresses Rho GTPases in human brain microvascular endothelial cells and inhibits adhesion and transendothelial migration of HIV-1 infected monocytes. J. Immunol. 180, 1854-1865
115. Gurley, C., Nichols, J., Liu, S, Phulwani, N. K., Esen, N. and Kielian, T. (2008) Microglia and astrocyte activation by Toll-like receptor ligands: modulation by PPAR-γ agonists. PPAR Res. 453120
116. Ji, Y., Liu, J., Wang, Z., Liu, N. and Gou, W. (2009) PPARγ agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway. Lab. Invest. 89, 887-902
117. Dzau, V. J. (2001) Tissue angiotensin and pathobiology of vascular disease: a unifying hypothesis. Hypertension 37, 1047-1052
118. Nickenig, G. and Harrison, D. G. (2002) The AT1-type angiotensin receptor in oxidative stress and atherogenesis: part I: oxidative stress and atherogenesis. Circulation 105, 393-396
119. Nickenig, G. (2002) Central role of the AT1-receptor in atherosclerosis. J. Hum. Hypertens. 16, S26-S33
120. Suzuki, Y., Ruiz-Ortega, M., Lorenzo, O., Ruperez, M., Esteban, V. and Egido, J. (2003) Inflammation and angiotensin II. Int. J. Biochem. Cell Biol. 35, 881-900
121. Dahlof, B., Devereux, R. B., Kjeldsen, S. E., Julius, S., Beevers, G., de Faire, U., Fyhrquist, F., Ibsen, H., Kristiansson, K., Lederballe-Pedersen, O. et al. (2002) LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359, 995-1003
122. Demers, C., McMurray, J. J., Swedberg, K., Pfeffer, M. A., Granger, C. B., Olofsson, B., McKelvie, R. S., Ostergren, J., Michelson, E. L., Johansson, P. A. et al. (2005) Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure. JAMA, J.Am. Med. Assoc. 294, 1794-1798
123. Mehta, J. L. (1998) Modulation of arterial thrombosis by angiotensin-converting enzyme inhibition and angiotensin II type 1-receptor blockade. Am. J. Cardiol. 82, 53S-56S
124. Heeneman, S., Sluimer, J. C. and Daemen, M.J.A.P. (2007) Angiotensin converting enzyme and vascular remodeling. Circ. Res. 101, 441-454
125. Tsutamoto, T., Wada, A., Maeda, K., Mabuchi, N., Hayashi, M., Tsutsui, T., Ohnishi, M., Sawaki, M., Fujii, M., Matsumoto, T. and Kinoshita, M. (2000) Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor α, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure. J. Am. Coll. Cardiol. 35, 714-721
126. Donaire, J. A. and Ruilope, L. M. (2007) Angiotensin receptor blockade in diabetic renal disease-focus on candesartan. Diabetes Res. Clin. Pract. 76, S22-S30
127. Ghiadoni, L., Virdis, A., Magagna, A., Taddei, S. and Salvetti, A. (2000) Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 35, 501-506
128. Koh,K.K., Ahn, J. Y., Han, S. H.,Kim,D. S., Jin, D. K., Kim, H. S., Shin, M. S., Ahn, T. H., Choi, I. S. and Shin, E. K. (2003) Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients. J. Am. Coll. Cardiol. 42, 905-910
129. Igarashi, M., Hirata, A., Yamaguchi, H., Tsuchiya, H., Ohnuma, H., Tominaga, M., Daimon, M. and Kato, T. (2001) Candesartan inhibits carotid intimal thickening and ameliorates insulin resistance in balloon-injured diabetic rats. Hypertension 38, 1255-1259
130. Koh, K. K., Quon, M. J., Han, S. H., Chung, W. J., Kim, J. A. and Shin, E. K. (2006) Vascular and metabolic effects of candesartan: insights from therapeutic interventions. J. Hypertens. (Suppl.) 24, S31-S38
131. Dohi, Y., Ohashi, M., Sugiyama, M., Takase, H., Sato, K. and Ueda, R. (2003) Candesartan reduces oxidative stress and inflammation in patients with essential hypertension. Hypertens. Res. 26, 691-697
132. Koh, K. K., Quon, M. J., Han, S. H., Chung,W. J., Lee, Y. and Shin, E. K. (2006) Anti-inflammatory and metabolic effects of candesartan in hypertensive patients. Int. J. Cardiol. 108, 96-100
133. Dasu, M. R., Riosvelasco, A. and Jialal, I. (2009) Candesartan inhibits Toll like receptor expression and activity both in vitro and in vivo. Atherosclerosis 202, 76-83
134. Shinohara, M., Hirata, K. I., Yamashita, T., Takaya, T., Sasaki, N., Shiraki, R., Ueyama, T., Emoto, N., Inoue, N., Yokoyama, M. and Kawashima, S. (2007) Local overexpression of Toll-like receptors at the vessel wall induces atherosclerotic lesion formation. Synergism of TLR2 and TLR4. Arterioscler. Thromb. Vasc. Biol. 27, 2384-2391
135. Medzhitov, R. and Janeway, Jr, C.A. (2002) Decoding the patterns of self and nonself by the innate immune system. Science 296, 298-300
136. Zhao, L., Lee, J. Y. and Hwang, D. H. (2011) Inhibition of pattern recognition receptor mediated inflammation by bioactive phytochemicals. Nutr. Rev. 69, 310-320
137. Hirai, S., Takahashi, N., Goto, T., Lin, S., Uemura, T., Yu, R. and Kawada, T. (2010) Functional food targeting the regulation of obesity-induced inflammatory responses and pathologies. Mediators Inflamm. 2010, 367838
138. Surh, Y. J. (2002) Anti-tumor promoting potential of selected spice ingredients with antioxidative and antiinflammatory activities: a short review. Food Chem. Toxicol. 40, 1091-1097
139. Yamamoto, T., Yoshimura, M., Yamaguchi, F., Kouchi, T., Tsuji, R., Saito, M., Obata, A. and Kikuchi, M. (2004) Anti-allergic activity of naringenin chalcone from a tomato skin extract. Biosci. Biotechnol. Biochem. 68, 1706-1711
140. Yeop, Han, C., Kargi, A. Y., Omer, M., Chan, C. K., Wabitsch, M., O'Brien, K. D., Wight, T. N. and Chait, A. (2010) Differential effect of saturated and unsaturated free fatty acids on the generation of monocyte adhesion and chemotactic factors by adipocytes: dissociation of adipocyte hypertrophy from inflammation. Diabetes 59, 386-396
141. Todoric, J., Laffler, M., Huber, J., Bilban,M., Reimers, M., Kadl, A., Zeyda, M., Waldhusl, W. and Stulnig, T. M. (2006) Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by omega-3 polyunsaturated fatty acids. Diabetologia 49, 2109-2119
142. Huber, J., Laffler, M., Bilban, M., Reimers, M., Kadl, A., Todoric, J., Zeyda, M., Geyeregger, R., Schreiner, M., Weichhart, T. et al. (2007) Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids. Int. J. Obes. 31, 1004-1013
143. Stulnig, T. M. (2003) Immunomodulation by polyunsaturated fatty acids: mechanisms and effects. Int. Arch. Allergy Immunol. 132, 310-321
144. Das, U. N. (2003) Folic acid says NO to vascular diseases. Nutrition 19, 686-692
145. Sheedy, F. J. and O'Neill, L. A. (2008) Adding fuel to fire: microRNAs as a new class of mediators of inflammation. Ann. Rheum. Dis. 67 (Suppl. 3), iii50-iii55
146. O'Neill, L. A., Sheedy, F. J. and McCoy, C. E. (2011) MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat. Rev. Immunol. 11, 163-175
147. Taganov, K. D., Boldin, M. P., Chang, K. J. and Baltimore, D. (2006) NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. U.S.A. 103, 12481-12486
148. Wang, Y., Devkota, S., Musch, M.W., Jabri, B., Nagler, C., Antonopoulos, D. A., Chervonsky, A. and Chang, E. B. (2010) Regional mucosa-associated microbiota determine physiological expression of TLR2 and TLR4 in murine colon. PLoS ONE 5, e13607