Human intestinal epithelial cells are broadly unresponsive to toll-like receptor 2-dependent bacterial ligands: Implications for host-microbial interactions in the gut

Journal of Immunology

Volumn 170, Issue 3, 2003, Pages 1406-1415

  Melmed, Gil ^a   Thomas, Lisa S ^a   Lee, Nahee ^a   Tesfay, Samuel Y ^a   Lukasek, Katie ^a   Michelsen, Kathrin S ^b   Zhou, Yuehua ^a   Hu, Bing ^a   Arditi, Moshe ^b   Abreu, Maria T ^a  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b BURNS AND ALLEN RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIGAND; PEPTIDOGLYCAN; TOLL INHIBITORY PROTEIN; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 6; UNCLASSIFIED DRUG;

ARTICLE; CELL ISOLATION; CONTROLLED STUDY; CYTOKINE RELEASE; FLOW CYTOMETRY; GENE ACTIVATION; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOFLUORESCENCE; INHIBITION KINETICS; INTESTINE EPITHELIUM CELL; INTESTINE FLORA; LAMINA PROPRIA; MOLECULAR DYNAMICS; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSGENIC ANIMAL;

EID: 0037307854     PISSN: 00221767     EISSN: None     Source Type: Journal    
DOI: 10.4049/jimmunol.170.3.1406     Document Type: Article

References (101)

1. Kim, J. M., L. Eckmann, T. C. Savidge, D. C. Lowe, T. Witthoft, and M. F. Kagnoff. 1998. Apoptosis of human intestinal epithelial cells after bacterial invasion. J. Clin. Invest. 102:1815.
2. Hecht, G. 1999. Innate mechanisms of epithelial host defense: spotlight on intestine. Am. J. Physiol. 277:C351.
3. Abreu-Martin, M. T., A. Vidrich, D. H. Lynch, and S. R. Targan. 1995. Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-α and ligation of Fas antigen. J. Immunol. 155:4147.
4. Eckmann, L., H. C. Jung, C. Schurer-Maly, A. Panja, E. Morzycka-Wroblewska, and M. F. Kagnoff. 1993. Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8. Gastroenterology 105:1689.
5. Jung, H. C., L. Eckmann, S. K. Yang, A. Panja, J. Fierer, E. Morzycka-Wroblewska, and M. F. Kagnoff. 1995. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J. Clin. Invest. 95:55.
6. Eckmann, L., M. F. Kagnoff, and M. T. Falco. 1994. Colonic epithelial cell lines as a source of interleukin-8: stimulation by inflammatory cytokines and bacterial lipopolysaccharide. Immunology 82:505.
7. Savkovic, S. D., A. Koutsouris, and G. Hecht. 1996. Attachment of a noninvasive enteric pathogen, enteropathogenic Escherichia coli, to cultured human intestinal epithelial monolayers induces transmigration of neutrophils. Infect. Immun. 64:4480.
8. Savkovic, S. D., A. Koutsouris, and G. Hecht. 1997. Activation of NF-κB in intestinal epithelial cells by enteropathogenic Escherichia coli. Am. J. Physiol. 273:C1160.
9. Schuerer-Maly, C. C., L. Eckmann, M. F. Kagnoff, M. T. Falco, and F. E. Maly. 1994. Colonic epithelial cell lines as a source of interleukin-8: stimulation by inflammatory cytokines and bacterial lipopolysaccharide. Immunology 81:85.
10. Wick, M. J., J. L. Madara, B. N. Fields, and S. J. Normark. 1991. Molecular cross talk between epithelial cells and pathogenic microorganisms. Cell 67:651.
11. Duchmann, R., I. Kaiser, E. Hermann, W. Mayet, K. Ewe, and K. H. Meyer zum Buschenfelde. 1995. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin. Exp. Immunol. 102:448.
12. Cohavy, O., D. Bruckner, L. K. Gordon, R. Misra, B. Wei, M. E. Eggena, S. R. Targan, and J. Braun. 2000. Colonic bacteria express an ulcerative colitis pANCA-related protein epitope. Infect. Immun. 68:1542.
13. Rutgeerts, P., K. Goboes, M. Peeters, M. Hiele, F. Penninckx, R. Aerts, R. Kerremans, and G. Vantrappen. 1991. Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet 338:771.
14. Janowitz, H. D., E. C. Croen, and D. B. Sachar. 1998. The role of the fecal stream in Crohn's disease: an historical and analytic review. Inflamm. Bowel. Dis. 4:29.
15. Sartor, R. B. 1998. Postoperative recurrence of Crohn's disease: the enemy is within the fecal stream. Gastroenterology 114:398.
16. Sandborn, W., R. McLeod, and D. Jewell. 2000. Pharmacotherapy for inducing and maintaining remission in pouchitis. Cochrane Database Syst. Rev. 2:CD001176.
17. Sartor, R. B. 2000. Probiotics in chronic pouchitis: restoring luminal microbial balance. Gastroenterology 119:584.
18. Gionchetti, P., F. Rizzello, A. Venturi, P. Brigidi, D. Matteuzzi, G. Bazzocchi, G. Poggioli, M. Miglioli, and M. Campieri. 2000. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119:305.
19. Rembacken, B. J., A. M. Snelling, P. M. Hawkey, D. M. Chalmers, and A. T. Axon. 1999. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354:635.
20. Prantera, C., F. Zannoni, M. L. Scribano, E. Berto, A. Andreoli, A. Kohn, and C. Luzi. 1996. An antibiotic regimen for the treatment of active Crohn's disease: a randomized, controlled clinical trial of metronidazole plus ciprofloxacin. Am. J. Gastroenterol. 91:328.
21. Hulten, K., A. Almashhrawi, F. A. El-Zaatari, and D. Y. Graham. 2000. Antibacterial therapy for Crohn's disease: a review emphasizing therapy directed against mycobacteria. Dig. Dis. Sci. 45:445.
22. Blumberg, R. S., L. J. Saubermann, and W. Strober. 2000. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr. Opin. Immunol. 12:226.
23. Sellon, R. K., S. Tonkonogy, M. Schultz, L. A. Dieleman, W. Grenther, E. Balish, D. M. Rennick, and R. B. Sartor. 1998. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66:5224.
24. Schultz, M., and R. B. Sartor. 2000. Probiotics and inflammatory bowel diseases. Am. J. Gastroenterol. 95:S19.
25. Rath, H. C., J. S. Ikeda, H. J. Linde, J. Scholmerich, K. H. Wilson, and R. B. Sartor. 1999. Varying cecal bacterial loads influences colitis and gastritis in HLA-B27 transgenic rats. Gastroenterology 116:310.
26. MacDonald, T. T., and S. Pettersson. 2000. Bacterial regulation of intestinal immune responses. Inflamm. Bowel. Dis. 6:116.
27. French, N., and S. Pettersson. 2000. Microbe-host interactions in the alimentary tract: the gateway to understanding inflammatory bowel disease. Gut 47:162.
28. Rath, H. C., M. Schultz, R. Freitag, L. A. Dieleman, F. Li, H. J. Linde, J. Scholmerich, and R. B. Sartor. 2001. Different subsets of enteric bacteria induce and perpetuate experimental colitis in rats and mice. Infect. Immun. 69:2277.
29. Mushegian, A., and R. Medzhitov. 2001. Evolutionary perspective on innate immune recognition. J. Cell Biol. 155:705.
30. Akira, S., K. Takeda, and T. Kaisho. 2001. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2:675.
31. Muzio, M., N. Polentarutti, D. Bosisio, M. K. Prahladan, and A. Mantovani. 2000. Toll-like receptors: a growing family of immune receptors that are differentially expressed and regulated by different leukocytes. J. Leukocyte Biol. 67:450.
32. Zhang, F. X., C. J. Kirschning, R. Mancinelli, X. P. Xu, Y. Jin, E. Faure, A. Mantovani, M. Rothe, M. Muzio, and M. Arditi. 1999. Bacterial lipopolysaccharide activates nuclear factor-κB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J. Biol. Chem. 274:7611.
33. Xu, Y., X. Tao, B. Shen, T. Horng, R. Medzhitov, J. L. Manley, and L. Tong. 2000. Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408:111.
34. Medzhitov, R., and C. Janeway Jr. 2000. The Toll receptor family and microbial recognition. Trends Microbiol. 8:452.
35. Wang, Q., R. Dziarski, C. J. Kirschning, M. Muzio, and D. Gupta. 2001. Micrococci and peptidoglycan activate TLR2→MyD88→IRAK→TRAF→ NIK→IKK→NF-κB signal transduction pathway that induces transcription of interleukin-8. Infect. Immun. 69:2270.
36. Poltorak, A., X. He, I. Smirnova, M. Y. Liu, C. V. Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in TLR4 gene. Science 282:2085.
37. Beutler, B. 2000. TLR4: central component of the sole mammalian LPS sensor. Curr. Opin. Immunol. 12:20.
38. Hoshino, K., O. Takeuchi, T. Kawai, H. Sanjo, T. Ogawa, Y. Takeda, K. Takeda, and S. Akira. 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.
39. Schwandner, R., R. Dziarski, H. Wesche, M. Rothe, and C. J. Kirschning. 1999. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. J. Biol. Chem. 274:17406.
40. Takeuchi, O., K. Hoshino, T. Kawai, H. Sanjo, H. Takada, T. Ogawa, K. Takeda, and S. Akira. 1999. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11:443.
41. Yoshimura, A., E. Lien, R. R. Ingalls, E. Tuomanen, R. Dziarski, and D. Golenbock. 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.
42. Lien, E., T. J. Sellati, A. Yoshimura, T. H. Flo, G. Rawadi, R. W. Finberg, J. D. Carroll, T. Espevik, R. R. Ingalls, J. D. Radolf, and D. T. Golenbock. 1999. Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J. Biol. Chem. 274:33419.
43. Opitz, B., N. W. Schroder, I. Spreitzer, K. S. Michelsen, C. J. Kirschning, W. Hallatschek, U. Zahringer, T. Hartung, U. B. Gobel, and R. R. Schumann. 2001. Toll-like receptor-2 mediates Treponema glycolipid and lipoteichoic acid-induced NF-κB translocation. J. Biol. Chem. 276:22041.
44. Means, T. K., B. W. Jones, A. B. Schromm, B. A. Shurtleff, J. A. Smith, J. Keane, D. T. Golenbock, S. N. Vogel, and M. J. Fenton. 2001. Differential effects of a Toll-like receptor antagonist on Mycobacterium tuberculosis-in duced macrophage responses. J. Immunol. 166:4074.
45. Jones, B. W., T. K. Means, K. A. Heldwein, M. A. Keen, P. J. Hill, J. T. Belisle, and M. J. Fenton. 2001. Different Toll-like receptor agonists induce distinct macrophage responses. J. Leukocyte Biol. 69:1036.
46. Takeuchi, O., K. Hoshino, and S. Akira. 2000. Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Sraphylococcus aureus infection. J. Immunol. 165:5392.
47. Lorenz, E., J. P. Mira, K. L. Cornish, N. C. Arbour, and D. A. Schwartz. 2000. A novel polymorphism in the Toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect. Immun. 68:6398.
48. Kang, T. J., and G. T. Chae. 2001. Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol. Med. Microbiol. 31:53.
49. Yang, R. B., M. R. Mark, A. Gray, A. Huang, M. H. Xie, M. Zhang, A. Goddard, W. I. Wood, A. L. Gurney, and P. J. Godowski. 1998. Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature 395:284.
50. Ozinsky, A., D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem. 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. USA 97:13766.
51. Ozinsky, A., K. D. Smith, D. Hume, and D. M. Underhill. 2000. Co-operative induction of pro-inflammatory signaling by Toll-like receptors. J. Endotoxin Res. 6:393.
52. Hajjar, A. M., D. S. O'Mahony, A. Ozinsky, D. M. Underhill, A. Aderem, S. J. Klebanoff, and C. B. Wilson. 2001. Cutting edge: functional interactions between Toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenolsoluble modulin. J. Imnumol. 166:15.
53. Means, T. K., S. Wang, E. Lien, A. Yoshimura, D. T. Golenbock, and M. J. Fenton. 1999. Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. J. Immunol. 163:3920.
54. Takeuchi, O., S. Sato, T. Horiuchi, K. Hoshino, K. Takeda, Z. Dong, R. L. Modlin, and S. Akira. 2002. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169:10.
55. Wyllie, D. H., E. Kiss-Toth, A. Visintin, S. C. Smith, S. Boussouf, D. M. Segal, G. W. Duff, and S. K. Dower. 2000. Evidence for an accessory protein function for Toll-like receptor 1 in anti-bacterial responses. J. Immunol. 165:7125.
56. Alexopoulou, L., V. Thomas, M. Schnare, Y. Lobet, J. Anguita, R. T. Schoen, R. Medzhitov, E. Fikrig, and R. A. Flavell. 2002. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat. Med. 8:878.
57. Spitzer, J. H., A. Visintin, A. Mazzoni, M. N. Kennedy, and D. M. Segal. 2002. Toll-like receptor 1 inhibits Toll-like receptor 4 signaling in endothelial cells. Eur. J. Immunol. 32:1182.
58. Burns, K., J. Clatworthy, L. Martin, F. Martinon, C. Plumpton, B. Maschera, A. Lewis, K. Ray, J. Tschopp, and F. Volpe. 2000. Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat. Cell Biol. 2:346.
59. Bulut, Y., E. Faure, L. Thomas, O. Equils, and M. Arditi. 2001. Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J. Immunol. 167:987.
60. Zhang, G., and S. Ghosh. 2002. Negative regulation of Toll-like receptor-mediated signaling by Tollip. J. Biol. Chem. 277:7059.
61. Dunne, C. 2001. Adaptation of bacteria to the intestinal niche: probiotics and gut disorder. Inflamm. Bowel Dis. 7:136.
62. Naidu, A. S., W. R. Bidlack, and R. A. Clemens. 1999. Probiotic spectra of lactic acid bacteria (LAB). Crit. Rev. Food Sci. Nutr. 39:13.
63. Rolfe, R. D. 2000. The role of probiotic cultures in the control of gastrointestinal health. J. Nutr. 130:396S.
64. Pryde, S. E., A. J. Richardson, C. S. Stewart, and H. J. Flint. 1999. Molecular analysis of the microbial diversity present in the colonic wall, colonic lumen, and cecal lumen of a pig. Appl. Environ. Microbiol. 65:5372.
65. Suau, A., R. Bonnet, M. Sutren, J. J. Godon, G. R. Gibson, M. D. Collins, and J. Dore, 1999. Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut. Appl. Environ. Microbiol. 65:4799.
66. Sartor, R. B., R. A. DeLa Cadena, K. D. Green, A. Stadnicki, S. W. Davis, J. H. Schwab, A. A. Adam, P. Raymond, and R. W. Colman. 1996. Selective kallikrein-kinin system activation in inbred rats differentially susceptible to granulomatous enterocolitis. Gastroenterology 110:1467.
67. Kandil, H. M., R. A. Argenzio, and R. B. Sartor. 2000. Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis. Dig. Dis. Sci. 45:2091.
68. Balish, E., and T. Warner. 2002. Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am. J. Pathol. 160:2253.
69. Kim, S. C., S. L. Tonkonogy, E. Balish, and R. B. Sartor. 2002. Bacterial antigen specific T-cell activation precedes intestinal inflammation in Enterococcus faecalis monoassociated IL-10 deficient mice. Gastroenterology 122:A692.
70. + T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: increased T helper cell type 1 response and ability to transfer disease. J. Exp. Med. 187:855.
71. Cario, E., and D. K. Podolsky. 2000. Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect. Immun. 68:7010.
72. Cario, E., D. Brown, M. McKee, K. Lynch-Devaney, G. Gerken, and D. K. Podolsky. 2002. Commensal-associated molecular patterns induce selective Toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium. Am. J. Pathol. 160:165.
73. Naik, S., E. J. Kelly, L. Meijer, S. Pettersson, and I. R. Sanderson. 2001. Absence of Toll-like receptor 4 explains endotoxin hyporesponsiveness in human intestinal epithelium. J. Pediatr. Gastroenterol. Nutr. 32:449.
74. Hausmann, M., S. Kiessling, S. Mestermann, G. Webb, T. Spottl, T. Andus, J. Scholmerich, H. Herfarth, K. Ray, W. Falk, and G. Rogler. 2002. Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 122:1987.
75. Abreu, M. T., A. A. Palladino, E. T. Arnold, R. S. Kwon, and J. A. McRoberts. 2000. Modulation of barrier function during Fas-mediated apoptosis in human intestinal epithelial cells. Gastroenterology 119:1524.
76. Dharmsathaphorn, K., J. A. McRoberts, K. G. Mandel, L. D. Tisdale, and H. Masui. 1984. A human colonic tumor cell line that maintains vectorial electrolyte transport. Am. J. Physiol. 246:G204.
77. Ades, E. W., F. J. Candal, R. A. Swerlick, V. G. George, S. Summers, D. C. Bosse, and T. J. Lawley. 1992. HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J. Invest. Dermatol. 99:683.
78. Faure, E., O. Equils, P. A. Sieling, L. Thomas, F. X. Zhang, C. J. Kirschning, N. Polentarutti, M. Muzio, and M. Arditi. 2000. Bacterial lipopolysaccharide activates NF-κB through Toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells: differential expression of TLR-4 and TLR-2 in endothelial cells. J. Biol. Chem. 275:11058.
79. Muller, M. R., S. D. Pfannes, M. Ayoub, P. Hoffmann, W. G. Bessler, and K. Mittenbuhler. 2001. Immunostimulation by the synthetic lipopeptide P3CSK4: TLR4-independent activation of the ERK1/2 signal transduction pathway in macrophages. Immunology 103:49.
80. Hornung, V., S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdorfer, T. Giese, S. Endres, and G. Hartmann. 2002. Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168:4531.
81. Cario, E., I. M. Rosenberg, S. L. Brandwein, P. L. Beck, H. C. Reinecker, and D. K. Podolsky. 2000. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J. Immunol. 164:966.
82. Faure, E., L. Thomas, H. Xu, A. Medvedev, O. Equils, and M. Arditi. 2001. Bacterial lipopolysaccharide and IFN-γ induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-κB activation. J. Immunol. 166:2018.
83. Abreu, M. T., P. Vora, E. Faure, L. S. Thomas, E. T. Arnold, and M. Arditi. 2001. Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J. Immunol. 167:1609.
84. 39 is critical for the recognition of Staphylococcus aureus peptidoglycan. J. Biol. Chem. 276:41350.
85. Rescigno, M., M. Urbano, B. Valzasina, M. Francolini, G. Rotta, R. Bonasio, F. Granucci, J. P. Kraehenbuhl, and P. Ricciardi-Castagnoli. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2:361.
86. Michel, O., A. M. Nagy, M. Schroeven, J. Duchateau, J. Neve, P. Fondu, and R. Sergysels. 1997. Dose-response relationship to inhaled endotoxin in normal subjects. Am. J. Respir. Crit. Care Med. 156:1157.
87. Rackley, R. R., S. K. Bandyopadhyay, S. Fazeli-Matin, M. S. Shin, and R. Appell. 1999. Immunoregulatory potential of urothelium: characterization of NF-κB signal transduction. J. Urol. 162:1812.
88. Shuto, T., A. Imasato, H. Jono, A. Sakai, H. Xu, T. Watanabe, D. D. Rixter, H. Kai, A. Andalibi, F. Linthicum, et al. 2002. Glucocorticoids synergistically enhance nontypeable Haemophilus influenzae-induced Toll-like receptor 2 expression via a negative cross-talk with p38 MAP kinase. J. Biol. Chem. 277:17263.
89. Fusunyan, R. D., N. N. Nanthakumar, M. E. Baldeon, and W. A. Walker. 2001. Evidence for an innate immune response in the immature human intestine: Toll-like receptors on fetal enterocytes. Pediatr. Res. 49:589.
90. Smith, P. D., L. E. Smythies, M. Mosteller-Barnum, D. A. Sibley, M. W. Russell, M. Merger, M. T. Sellers, J. M. Orenstein, T. Shimada, M. F. Graham, and H. Kubagawa. 2001. Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J. Immunol. 167:2651.
91. Iwaki, D., H. Mitsuzawa, S. Murakami, H. Sano, M. Konishi, T. Akino, and Y. Kuroki. 2002. The extracellular Toll-like receptor 2 domain directly binds peptidoglycan derived from Staphylococcus aureus. J. Biol. Chem. 277:24315.
92. Daig, R., G. Rogler, E. Aschenbrenner, D. Vogl, W. Falk, V. Gross, J. Scholmerich, and T. Andus. 2000. Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6. Gut 46:350.
93. Nielsen, O. H., P. Gionchetti, M. Ainsworth, B. Vainer, M. Campieri, N. Borregaard, and L. Kjeldsen. 1999. Rectal dialysate and fecal concentrations of neutrophil gelatinase-associated lipocalin, interleukin-8, and tumor necrosis factor-α in ulcerative colitis. Am. J. Gastroenterol. 94:2923.
94. Jobin, C., and R. B. Sartor. 2000. NF-κB signaling proteins as therapeutic targets for inflammatory-bowel diseases. Inflamm. Bowel. Dis. 6:206.
95. Madara, J. L., and K. Dharmsathaphorn. 1985. Occluding junction structure-function relationships in a cultured epithelial monolayer. J. Cell Biol. 101:2124.
96. Merlin, D., A. Steel, A. T. Gewirtz, M. St-Tahar, M. A. Hediger, and J. L. Madara. 1998. hPepT1-mediated epithelial transport of bacteria-derived chemotactic peptides enhances neutrophil-epithelial interactions. J. Clin. Invest. 102:2011.
97. Musch, M. W., K. Sugi, D. Straus, and E. B. Chang. 1999. Heat-shock protein 72 protects against oxidant-induced injury of barrier function of human colonic epithelial Caco2/bbe cells. Gastroenterology 117:115.
98. Li, M., D. F. Carpio, Y. Zheng, P. Bruzzo, V. Singh, F. Ouaaz, R. M. Medzhitov, and A. A. Beg. 2001. An essential role of the NF-κB/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells. J. Immunol. 166:7128.
99. Michelsen, K. S., A. Aicher, M. Mohaupt, T. Hartung, S. Dimmeler, C. J. Kirschning, and R. R. Schumann. 2001. The role of Toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCS): peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2. J. Biol. Chem. 276:25680.
100. Birchler, T., R. Seibl, K. Buchner, S. Loeliger, R. Seger, J. P. Hossle, A. Aguzzi, and R. P. Lauener. 2001. Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human β-defensin 2 in response to bacterial lipoprotein. Eur. J. Immunol. 31:3131.
101. Thoma-Uszynski, S., S. M. Kiertscher, M. T. Ochoa, D. A. Bouis, M. V. Norgard, K. Miyake, P. J. Godowski, M. D. Roth, and R. L. Modlin. 2000. Activation of Toll-like receptor 2 on human dendritic cells triggers induction of IL-12, but not IL-10. J. Immunol. 165:3804.