Toll-like receptor 2 is required for LPS-induced toll-like receptor 4 signaling and inhibition of ion transport in renal thick ascending limb

Journal of Biological Chemistry

Volumn 287, Issue 24, 2012, Pages 20208-20220

  Good, David W ^a   George, Thampi ^a   Watts III, Bruns A ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BASOLATERAL ADDITION; BASOLATERAL MEMBRANES; CO-IMMUNOPRECIPITATIONS; DUAL ROLE; ERK ACTIVATION; ESCHERICHIA COLI K12; INTRACELLULAR SIGNALS; ION TRANSPORTS; MEDULLARY THICK ASCENDING LIMBS; NEW MECHANISMS; SIGNALING PATHWAYS; TOLL-LIKE RECEPTOR 2; TOLL-LIKE RECEPTOR 4; WILD TYPES;

ESCHERICHIA COLI; MAMMALS; PHOSPHORYLATION;

LIGANDS;

BICARBONATE; CD14 ANTIGEN; ESCHERICHIA COLI LIPOPOLYSACCHARIDE; LIGAND; MITOGEN ACTIVATED PROTEIN KINASE; MYELOID DIFFERENTIATION FACTOR 88; PROTEIN MD 2; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4;

ABSORPTION; ANIMAL CELL; ARTICLE; BASOLATERAL MEMBRANE; CELL ISOLATION; CONTROLLED STUDY; ENZYME PHOSPHORYLATION; ESCHERICHIA COLI K 12; HENLE LOOP; IMMUNOPRECIPITATION; ION TRANSPORT; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; WILD TYPE;

ANIMALS; ANTIGENS, CD14; CARBONATES; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; GENE EXPRESSION REGULATION; ION TRANSPORT; KIDNEY MEDULLA; LIPOPOLYSACCHARIDES; MALE; MAP KINASE SIGNALING SYSTEM; MICE; MICE, KNOCKOUT; MYELOID DIFFERENTIATION FACTOR 88; PHOSPHORYLATION; RATS; RATS, SPRAGUE-DAWLEY; TOLL-LIKE RECEPTOR 2; TOLL-LIKE RECEPTOR 4;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; MUS; POSIBACTERIA;

EID: 84862027265     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.336255     Document Type: Article

References (88)

1. Levy, E. M., Viscoli, C. M., and Horwitz, R. I. (1996) The effect of acute renal failure on mortality. A cohort analysis. JAMA 275, 1489-1494 (Pubitemid 26140761)
2. Cohen, J. (2002) The immunopathogenesis of sepsis. Nature 420, 885-891
3. Schrier, R. W., and Wang, W. (2004) Acute renal failure and sepsis. NEJM 351, 159-169
4. Doi, K., Leelahavanichkul, A., Yuen, P. S., and Star, R. A. (2009) Animal models of sepsis and sepsis-induced kidney injury. J. Clin. Invest. 119, 2868-2878
5. Klenzak, J., and Himmelfarb, J. (2005) Sepsis and the kidney. Crit. Care Clin. 21, 211-222 (Pubitemid 40386750)
6. El-Achkar, T. M., Hosein, M., and Dagher, P. C. (2008) Pathways of renal injury in systemic gram-negative sepsis. Eur. J. Clin. Invest. 38, 39-44
7. Russell, J. A., Singer, J., Bernard, G. R., Wheeler, A., Fulkerson, W., Hudson, L., Schein, R., Summer, W., Wright, P., and Walley, K. R. (2000) Changing pattern of organ dysfunction in early human sepsis is related to mortality. Crit. Care Med. 28, 3405-3411
8. Oppert, M., Engel, C., Brunkhorst, F. M., Bogatsch, H., Reinhart, K., Frei, U., Eckardt, K. U., Loeffler, M., and John, S. (2008) Acute renal failure in patients with severe sepsis and septic shock. A significant independent risk factor for mortality. Results from the German Prevalence Study. Nephrol. Dial. Transplant. 23, 904-909 (Pubitemid 351767542)
9. Austgen, T. R., Chen, M. K., Moore, W., and Souba, W. W. (1991) Endotoxin and renal glutamine metabolism. Arch. Surg. 126, 23-27
10. Grinevich, V., Knepper, M. A., Verbalis, J., Reyes, I., and Aguilera, G. (2004) Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla. Kidney Int. 65, 54-62 (Pubitemid 38037491)
11. Schmidt, C., Höcherl, K., and Bucher, M. (2007) Regulation of renal glucose transporters during severe inflammation. Am. J. Physiol. Renal Physiol. 292, F804-F811 (Pubitemid 46220549)
12. Wang, W., Li, C., Summer, S. N., Falk, S., Wang, W., Ljubanovic, D., and Schrier, R. W. (2008) Role of AQP1 in endotoxemia-induced acute kidney injury. Am. J. Physiol. Renal Physiol. 294, F1473-F1480
13. Olesen, E. T., de Seigneux, S., Wang, G., Lütken, S. C., Frøkiaiaer, J., Kwon, T. H., and Nielsen, S. (2009) Rapid and segmental specific dysregulation of AQP2, S256-pAQP2, and renal sodium transporters in rats with LPS-induced endotoxemia. Nephrol. Dial. Transplant. 24, 2338-2349
14. Good, D. W., George, T., and Watts, B. A., 3rd (2009) Lipopolysaccharide directly alters renal tubule transport through distinct TLR4-dependent pathways in basolateral and apical membranes. Am. J. Physiol. Renal Physiol. 297, F866-F874
15. - absorption by bacterial lipoprotein in medullary thick ascending limb. Am. J. Physiol. Renal Physiol. 299, F536-F544
16. Kraut, J. A., and Kurtz, I. (2001) Use of base in the treatment of severe acidemic states. Am. J. Kidney Dis. 38, 703-727
17. Kellum, J. A., Song, M., and Venkataraman, R. (2004) Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis. Chest 125, 243-248 (Pubitemid 38114589)
18. Baumgart, K., Radermacher, P., Calzia, E., and Hauser, B. (2008) Pathophysiology of tissue acidosis in septic shock. Blocked microcirculation or impaired cellular respiration? Crit. Care Med. 36, 640-642 (Pubitemid 351158656)
19. Gómez, J., García-Vázquez, E., Baños, R., Canteras, M., Ruiz, J., Baños, V., Herrero, J. A., and Valdés, M. (2007) Predictors of mortality in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. the role of empiric antibiotic therapy. Eur. J. Clin. Microbiol. Infect. Dis. 26, 239-245
20. Lee, S. W., Hong, Y. S., Park, D. W., Choi, S. H., Moon, S. W., Park, J. S., Kim, J. Y., and Baek, K. J. (2008) Lactic acidosis not hyperlactatemia as a predictor of in hospital mortality in septic emergency patients. Emerg. Med. J. 25, 659-665
21. Akira, S., Uematsu, S., and Takeuchi, O. (2006) Pathogen recognition and innate immunity. Cell 124, 783-801 (Pubitemid 43261452)
22. Kawai, T., and Akira, S. (2010) The role of pattern-recognition receptors in innate immunity. Update on Toll-like receptors. Nat. Immunol. 11, 373-384
23. Poltorak, A., He, X., Smirnova, I., Liu, M. Y., Van Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi- Castagnoli, P., Layton, B., and Beutler, B. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice. Mutations in Tlr4 gene. Science 282, 2085-2088 (Pubitemid 29001265)
24. Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., and Akira, S. (1999) Cutting edge. Toll-like receptor 4 (TLR4)- deficient mice are hyporesponsive to lipopolysaccharide. Evidence for TLR4 as the Lps gene product. J. Immunol. 162, 3749-3752 (Pubitemid 29314747)
25. Heine, H., Kirschning, C. J., Lien, E., Monks, B. G., Rothe, M., and Golenbock, D. T. (1999) Cutting edge. Cells that carry a null allele for Toll-like receptor 2 are capable of responding to endotoxin. J. Immunol. 162, 6971-6975 (Pubitemid 29277661)
26. Qureshi, S. T., Larivière, L., Leveque, G., Clermont, S., Moore, K. J., Gros, P., and Malo, D. (1999) Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4) J. Exp. Med. 189, 615-625 (Pubitemid 29193362)
27. Hirschfeld, M., Ma, Y., Weis, J. H., Vogel, S. N., and Weis, J. J. (2000) Cutting edge. Repurification of lipopolysaccharide eliminates signaling through both human and murine Toll-like receptor 2. J. Immunol. 165, 618-622 (Pubitemid 30484724)
28. Tapping, R. I., and Tobias, P. S. (2003) Mycobacterial lipoarabinomannan mediates physical interactions between TLR1 and TLR2 to induce signaling. J. Endotoxin Res. 9, 264-268 (Pubitemid 36874538)
29. Beutler, B. (2000) Tlr4. Central component of the sole mammalian LPS sensor. Curr. Opin. Immunol. 12, 20-26
30. Dixon, D. R., and Darveau, R. P. (2005) Lipopolysaccharide heterogeneity. Innate host responses to bacterial modification of lipid A structure. J. Dent. Res. 84, 584-595 (Pubitemid 43827837)
31. Kawai, T., and Akira, S. (2006) TLR signaling. Cell Death Differ. 13, 816-825
32. - absorption through TLR4/ MyD88-dependent ERK activation in medullary thick ascending limb. Am. J. Physiol. Cell Physiol. 301, C1296-C1306
33. Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., Takeda, K., and Akira, S. (1999) Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11, 443-451 (Pubitemid 29504199)
34. Yoshimura, A., Lien, E., Ingalls, R. R., Tuomanen, E., Dziarski, R., and Golenbock, D. (1999) Cutting edge. Recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 163, 1-5 (Pubitemid 29295815)
35. Takeuchi, O., Hoshino, K., and Akira, S. (2000) Cutting edge. TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J. Immunol. 165, 5392-5396
36. Ozinsky, A., Underhill, D. M., Fontenot, J. D., Hajjar, A. M., Smith, K. D., Wilson, C. B., Schroeder, L., and Aderem, A. (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proc. Natl. Acad. Sci. U.S.A. 97, 13766-13771
37. Alexopoulou, L., Thomas, V., Schnare, M., Lobet, Y., Anguita, J., Schoen, R. T., Medzhitov, R., Fikrig, E., and Flavell, R. A. (2002) Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat. Med. 8, 878-884
38. Schröder, N. W., Morath, S., Alexander, C., Hamann, L., Hartung, T., Zähringer, U., Göbel, U. B., Weber, J. R., and Schumann, R. R. (2003) Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide- binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J. Biol. Chem. 278, 15587-15594 (Pubitemid 36799667)
39. Takeuchi, O., Kawai, T., Mühlradt, P. F., Morr, M., Radolf, J. D., Zychlinsky, A., Takeda, K., and Akira, S. (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13, 933-940 (Pubitemid 32685205)
40. Takeuchi, O., Sato, S., Horiuchi, T., Hoshino, K., Takeda, K., Dong, Z., Modlin, R. L., and Akira, S. (2002) Cutting edge. Role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169, 10-14 (Pubitemid 34686113)
41. Sandor, F., Latz, E., Re, F., Mandell, L., Repik, G., Golenbock, D. T., Espevik, T., Kurt-Jones, E. A., and Finberg, R. W. (2003) Importance of extraand intracellular domains of TLR1 and TLR2 in NFκ B signaling. J. Cell Biol. 162, 1099-1110 (Pubitemid 37174192)
42. Lee, H. K., Dunzendorfer, S., and Tobias, P. S. (2004) Cytoplasmic domain-mediated dimerizations of Toll-like receptor 4 observed by β-lactamase enzyme fragment complementation. J. Biol. Chem. 279, 10564-10574 (Pubitemid 38372668)
43. Good, D. W. (1990) Inhibition of bicarbonate absorption by peptide hormones and cyclic adenosine monophosphate in rat medullary thick ascending limb. J. Clin. Invest. 85, 1006-1013
44. + exchanger NHE1 null mutant mice. Am. J. Physiol. Renal Physiol. 287, F1244-F1249
45. - absorption by nerve growth factor in MTAL. Am. J. Physiol. Renal Physiol. 282, F1056-F1063
46. - absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb. J. Biol. Chem. 283, 26602-26611
47. + exchangers. Am. J. Physiol. Renal Physiol. 301, F334-F343
48. - cotransporter, BSC-1. Am. J. Physiol. 271, F619-F628
49. Kim, G. H., Ecelbarger, C., Knepper, M. A., and Packer, R. K. (1999) Regulation of thick ascending limb ion transporter abundance in response to altered acid/base intake. J. Am. Soc. Nephrol. 10, 935-942 (Pubitemid 29203079)
50. - absorption in thick ascending limb via PI 3-kinase. Am. J. Physiol. Cell Physiol. 279, C1443-C1454
51. - absorption through actin cytoskeleton remodeling in renal thick ascending limb. J. Biol. Chem. 280, 11439-11447
52. - absorption via a nongenomic ERK-dependent pathway in medullary thick ascending limb. Am. J. Physiol. Renal Physiol. 291, F1005-F1013
53. + transporter subcellular distribution, abundance, and phosphorylation status. Am. J. Physiol. Renal Physiol. 295, F1003-F1016
54. Laghmani, K., Borensztein, P., Ambühl, P., Froissart, M., Bichara, M., Moe, O. W., Alpern, R. J., and Paillard, M. (1997) Chronic metabolic acidosis enhances NHE-3 protein abundance and transport activity in the rat thick ascending limb by increasing NHE-3 mRNA. J. Clin. Invest. 99, 24-30 (Pubitemid 27058290)
55. Shimazu, R., Akashi, S., Ogata, H., Nagai, Y., Fukudome, K., Miyake, K., and Kimoto, M. (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189, 1777-1782 (Pubitemid 29272694)
56. Schromm, A. B., Lien, E., Henneke, P., Chow, J. C., Yoshimura, A., Heine, H., Latz, E., Monks, B. G., Schwartz, D. A., Miyake, K., and Golenbock, D. T. (2001) Molecular genetic analysis of an endotoxin nonresponder mutant cell line. A point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling. J. Exp. Med. 194, 79-88 (Pubitemid 32660439)
57. Nagai, Y., Akashi, S., Nagafuku, M., Ogata, M., Iwakura, Y., Akira, S., Kitamura, T., Kosugi, A., Kimoto, M., and Miyake, K. (2002) Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol. 3, 667-672 (Pubitemid 34752476)
58. Visintin, A., Latz, E., Monks, B. G., Espevik, T., and Golenbock, D. T. (2003) Lysines 128 and 132 enable lipopolysaccharide binding to MD-2, leading to Toll-like receptor-4 aggregation and signal transduction. J. Biol. Chem. 278, 48313-48320 (Pubitemid 37523286)
59. Haziot, A., Chen, S., Ferrero, E., Low, M. G., Silber, R., and Goyert, S. M. (1988) The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J. Immunol. 141, 547-552
60. Lee, J. D., Kato, K., Tobias, P. S., Kirkland, T. N., and Ulevitch, R. J. (1992) Transfection of CD14 into 70Z/3 cells dramatically enhances the sensitivity to complexes of lipopolysaccharide (LPS) and LPS-binding protein. J. Exp. Med. 175, 1697-1705
61. Wright, S. D. (1995) CD14 and innate recognition of bacteria. J. Immunol. 155, 6-8
62. Lien, E., and Ingalls, R. R. (2002) Toll-like receptors. Crit. Care Med. 30, S1-S11 (Pubitemid 34131156)
63. Prohinar, P., Re, F., Widstrom, R., Zhang, D., Teghanemt, A., Weiss, J. P., and Gioannini, T. L. (2007) Specific high affinity interactions of monomeric endotoxin.protein complexes with Toll-like receptor 4 ectodomain. J. Biol. Chem. 282, 1010-1017 (Pubitemid 47076551)
64. Brightbill, H. D., Libraty, D. H., Krutzik, S. R., Yang, R. B., Belisle, J. T., Bleharski, J. R., Maitland, M., Norgard, M. V., Plevy, S. E., Smale, S. T., Brennan, P. J., Bloom, B. R., Godowski, P. J., and Modlin, R. L. (1999) Host defense mechanisms triggered by microbial lipoproteins through Toll-like receptors. Science 285, 732-736
65. Schwandner, R., Dziarski, R., Wesche, H., Rothe, M., and Kirschning, C. J. (1999) Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. J. Biol. Chem. 274, 17406-17409
66. Manukyan, M., Triantafilou, K., Triantafilou, M., Mackie, A., Nilsen, N., Espevik, T., Wiesmüller, K. H., Ulmer, A. J., and Heine, H. (2005) Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2, and TLR1. Eur. J. Immunol. 35, 911-921 (Pubitemid 40425547)
67. Beutler, B. (2005) The Toll-like receptors. Analysis by forward genetic methods. Immunogenetics 57, 385-392
68. Pfeiffer, A., Böttcher, A., Orsó, E., Kapinsky, M., Nagy, P., Bodnár, A., Spreitzer, I., Liebisch, G., Drobnik, W., Gempel, K., Horn, M., Holmer, S., Hartung, T., Multhoff, G., Schütz, G., Schindler, H., Ulmer, A. J., Heine, H., Stelter, F., Schütt, C., Rothe, G., Szöllôsi, J., Damjanovich, S., and Schmitz, G. (2001) Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts. Eur. J. Immunol. 31, 3153-3164 (Pubitemid 33100507)
69. Triantafilou, M., Miyake, K., Golenbock, D. T., and Triantafilou, K. (2002) Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation. J. Cell Sci. 115, 2603-2611 (Pubitemid 34778077)
70. Triantafilou, M., Manukyan, M., Mackie, A., Morath, S., Hartung, T., Heine, H., and Triantafilou, K. (2004) Lipoteichoic acid and Toll-like receptor 2 internalization and targeting to the Golgi are lipid raft-dependent. J. Biol. Chem. 279, 40882-40889 (Pubitemid 39287687)
71. Hirschfeld, M., Weis, J. J., Toshchakov, V., Salkowski, C. A., Cody, M. J., Ward, D. C., Qureshi, N., Michalek, S. M., and Vogel, S. N. (2001) Signaling by Toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect. Immun. 69, 1477-1482 (Pubitemid 32187597)
72. Werts, C., Tapping, R. I., Mathison, J. C., Chuang, T. H., Kravchenko, V., Saint Girons, I., Haake, D. A., Godowski, P. J., Hayashi, F., Ozinsky, A., Underhill, D. M., Kirschning, C. J., Wagner, H., Aderem, A., Tobias, P. S., and Ulevitch, R. J. (2001) Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nat. Immunol. 2, 346-352 (Pubitemid 33706346)
73. Morr, M., Takeuchi, O., Akira, S., Simon, M. M., and Mühlradt, P. F. (2002) Differential recognition of structural details of bacterial lipopeptides by Toll-like receptors. Eur. J. Immunol. 32, 3337-3347 (Pubitemid 36024371)
74. Hajjar, A. M., O'Mahony, D. S., Ozinsky, A., Underhill, D. M., Aderem, A., Klebanoff, S. J., and Wilson, C. B. (2001) Cutting edge. Functional interactions between Toll-like receptor (TLR)2 and TLR1 or TLR6 in response to phenol-soluble modulin. J. Immunol. 166, 15-19 (Pubitemid 32038411)
75. Chowdhury, P., Sacks, S. H., and Sheerin, N. S. (2006) Toll-like receptors TLR2 and TLR4 initiate the innate immune response of the renal tubular epithelium to bacterial products. Clin. Exp. Immunol. 145, 346-356 (Pubitemid 44060126)
76. Lee, M. S., and Kim, Y. J. (2007) Signaling pathways downstream of pattern-recognition receptors and their cross-talk. Annu. Rev. Biochem. 76, 447-480
77. Triantafilou, M., Brandenburg, K., Kusumoto, S., Fukase, K., Mackie, A., Seydel, U., and Triantafilou, K. (2004) Combinational clustering of receptors following stimulation by bacterial products determines lipopolysaccharide responses. Biochem. J. 381, 527-536 (Pubitemid 38969699)
78. Triantafilou, K., Triantafilou, M., and Dedrick, R. L. (2001) A CD14-independent LPS receptor cluster. Nat. Immunol. 2, 338-345 (Pubitemid 33706345)
79. - absorption in medullary thick ascending limb through a TLR4-ERK pathway upregulated by sepsis. J. Am. Soc. Nephrol. 22, 80A
80. Lotze, M. T., and Tracey, K. J. (2005) High-mobility group box 1 protein (HMGB1). Nuclear weapon in the immune arsenal. Nat. Rev. Immunol. 5, 331-342 (Pubitemid 40516158)
81. Vabulas, R. M., Ahmad-Nejad, P., da Costa, C., Miethke, T., Kirschning, C. J., Häcker, H., and Wagner, H. (2001) Endocytosed HSP60s use Toll-like receptor 2 (TLR2) and TLR4 to activate the Toll/interleukin-1receptor signaling pathway in innate immune cells. J. Biol. Chem. 276, 31332-31339 (Pubitemid 37385004)
82. Lim, S. W., Li, C., Ahn, K. O., Kim, J., Moon, I. S., Ahn, C., Lee, J. R., and Yang, C. W. (2005) Cyclosporine-induced renal injury induces Toll-like receptor and maturation of dendritic cells. Transplantation 80, 691-699 (Pubitemid 41379412)
83. Leemans, J. C., Stokman, G., Claessen, N., Rouschop, K. M., Teske, G. J., Kirschning, C. J., Akira, S., van der Poll, T., Weening, J. J., and Florquin, S. (2005) Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney. J. Clin. Invest. 115, 2894-2903 (Pubitemid 41434417)
84. Brown, H. J., Lock, H. R., Sacks, S. H., and Robson, M. G. (2006) TLR2 stimulation of intrinsic renal cells in the induction of immune-mediated glomerulonephritis. J. Immunol. 177, 1925-1931 (Pubitemid 44092533)
85. Wu, H., Chen, G., Wyburn, K. R., Yin, J., Bertolino, P., Eris, J. M., Alexander, S. I., Sharland, A. F., and Chadban, S. J. (2007) TLR4 activation mediates kidney ischemia/reperfusion injury. J. Clin. Invest. 117, 2847-2859 (Pubitemid 47529615)
86. Shigeoka, A. A., Holscher, T. D., King, A. J., Hall, F. W., Kiosses, W. B., Tobias, P. S., Mackman, N., and McKay, D. B. (2007) TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways. J. Immunol. 178, 6252-6258 (Pubitemid 46717408)
87. Zhang, B., Ramesh, G., Uematsu, S., Akira, S., and Reeves, W. B. (2008) TLR4 signaling mediates inflammation and tissue injury in nephrotoxicity. J. Am. Soc. Nephrol. 19, 923-932
88. Leemans, J. C., Butter, L. M., Pulskens, W. P., Teske, G. J., Claessen, N., van der Poll, T., and Florquin, S. (2009) The role of Toll-like receptor 2 in inflammation and fibrosis during progressive renal injury. PLoS One 4, e5704