Toll-like receptor 4 (TLR4) modulation by synthetic and natural compounds: An update

Journal of Medicinal Chemistry

Volumn 57, Issue 9, 2014, Pages 3612-3622

  Peri, Francesco ^a   Calabrese, Valentina ^a  

^a UNIVERSITY OF MILANO BICOCCA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CD14 ANTIGEN; CHEMOKINE; CYTOKINE; DANGER ASSOCIATED MOLECULAR PATTERN; ENDOTOXIN; HOMODIMER; IMMUNOMODULATING AGENT; LIGAND; LIPID A DERIVATIVE; NATURAL PRODUCT; PROTEIN MD 2; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

BINDING AFFINITY; CYTOKINE PRODUCTION; IMMUNE RESPONSE; IMMUNOMODULATION; INFLAMMATION; NONHUMAN; RECEPTOR BLOCKING; RECEPTOR UPREGULATION; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

ANIMALS; BIOLOGICAL PRODUCTS; HUMANS; LIPID A; MICE; STRUCTURE-ACTIVITY RELATIONSHIP; TOLL-LIKE RECEPTOR 4;

EID: 84900320851     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm401006s     Document Type: Review

References (70)

1. Akira, S.; Takeda, K. Toll-like receptor signaling Nat. Rev. Immunol. 2004, 4, 499-511
2. Poltorak, A.; He, X.; Smirnova, I.; Liu, M.; Van Huffel, C.; Du, X.; Birdwell, D.; Alejos, E.; Silva, M.; Galanos, C.; Freudenberg, M.; Ricciardi-Castagnoli, P.; Layton, B.; Beutler, B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene Science 1998, 282, 2085-2088
3. Beutler, B.; Du, X.; Poltorak, A. Identification of Toll-like receptor 4 (Tlr4) as the sole conduit for LPS signal transduction: genetic and evolutionary studies J. Endotoxin Res. 2001, 7, 277-280
4. Jeong, E.; Lee, J. Y. Intrinsic and extrinsic regulation of innate immune receptors Yonsei Med. J. 2011, 52, 379-392
5. Lucas, K.; Maes, M. Role of the Toll like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway Mol. Neurobiol. 2013, 48, 190-204
6. Cribbs, S.; Martin, G. Expanding the global epidemiology of sepsis Crit. Care Med. 2007, 35, 2646-2648
7. Jerala, R. Structural biology of the LPS recognition Int. J. Med. Microbiol. 2007, 297, 353-363
8. Schumann, R.; Leong, S.; Flaggs, G.; Gray, P.; Wright, S.; Mathison, J.; Tobias, P.; Ulevitch, R. Structure and function of lipopolysaccharide binding protein Science 1990, 249, 1429-1431
9. Wright, S.; Ramos, R.; Tobias, P.; Ulevitch, R.; Mathison, J. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein Science 1990, 249, 1431-1433
10. 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
11. Park, B.; Song, D.; Kim, H.; Choi, B.; Lee, H.; Lee, J. The structural basis of lipopolysaccharide recognition by the TLR4.MD-2 complex Nature 2009, 458, 1191-1195
12. Ohto, U.; Fukase, K.; Miyake, K.; Shimizu, T. Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2 Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 7421-7426
13. Yu, L.; Phillips, R. L.; Zhang, D.; Teghanemt, A.; Weiss, J. P.; Gioannini, T. L. NMR studies of hexaacylated endotoxin bound to wild-type and F126A mutant MD-2 and MD-2·TLR4 ectodomain complexes J. Biol. Chem. 2012, 287, 16346-16355
14. Chun, K. H.; Seong, S. Y. CD14 but not MD-2 transmit signals from DAMP Int. Immunopharmacol. 2010, 10, 98-106
15. Needham, B. D.; Trent, M. S. Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis Nat. Rev. Microbiol. 2013, 11, 467-481
16. Kim, H.; Park, B.; Kim, J.; Kim, S.; Lee, J.; Oh, S.; Enkhbayar, P.; Matsushima, N.; Lee, H.; Yoo, O.; Lee, J. Crystal structure of the TLR4.MD-2 complex with bound endotoxin antagonist eritoran Cell 2007, 130, 906-917
17. Bowen, W. S.; Minns, L. A.; Johnson, D. A.; Mitchell, T. C.; Hutton, M. M.; Evans, J. T. Selective TRIF-dependent signaling by a synthetic toll-like receptor 4 agonist Sci. Signaling 2012, 5, 13-20
18. Mata-Haro, V.; Cekic, C.; Martin, M.; Chilton, P. M.; Casella, C. R.; Mitchell, T. C. The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4 Science 2007, 316, 1628-1632
19. Peri, F.; Piazza, M. Therapeutic targeting of innate immunity with Toll-like receptor 4 (TLR4) antagonists Biotechnol. Adv. 2012, 30, 251-260
20. Wang, X.; Smith, C.; Yin, H. Targeting Toll-like receptors with small molecule agents Chem. Soc. Rev. 2013, 42, 4859-4866
21. Schromm, A.; Howe, J.; Ulmer, A.; Wiesmüller, K.; Seyberth, T.; Jung, G.; Rössle, M.; Koch, M.; Gutsmann, T.; Brandenburg, K. Physicochemical and biological analysis of synthetic bacterial lipopeptides: validity of the concept of endotoxic conformation J. Biol. Chem. 2007, 282, 11030-11037
22. Ohto, U.; Fukase, K.; Miyake, K.; Satow, Y. Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa Science 2007, 316, 1632-1634
23. Dunn-Siegrist, I.; Tissières, P.; Drifte, G.; Bauer, J.; Moutel, S.; Pugin, J. Toll-like receptor activation of human cells by synthetic triacylated lipid A-like molecules J. Biol. Chem. 2012, 287, 16121-16131
24. Piazza, M.; Calabrese, V.; Damore, G.; Cighetti, R.; Gioannini, T.; Weiss, J.; Peri, F. A synthetic lipid A mimetic modulates human TLR4 activity ChemMedChem 2012, 7, 213-217
25. Lewicky, J. D.; Ulanova, M.; Jiang, Z. H. Improving the immunostimulatory potency of diethanolamine-containing lipid A mimics Bioorg. Med. Chem. 2013, 21, 2199-2209
26. Piazza, M.; Rossini, C.; Della Fiorentina, S.; Pozzi, C.; Comelli, F.; Bettoni, I.; Fusi, P.; Costa, B.; Peri, F. Glycolipids and benzylammonium lipids as novel antisepsis agents: synthesis and biological characterization J. Med. Chem. 2009, 52, 1209-1213
27. Bettoni, I.; Comelli, F.; Rossini, C.; Granucci, F.; Giagnoni, G.; Peri, F.; Costa, B. Glial TLR4 receptor as new target to treat neuropathic pain: efficacy of a new receptor antagonist in a model of peripheral nerve injury in mice Glia 2008, 56, 1312-1319
28. Piazza, M.; Yu, L.; Teghanemt, A.; Gioannini, T.; Weiss, J.; Peri, F. Evidence of a specific interaction between new synthetic antisepsis agents and CD14 Biochemistry 2009, 48, 12337-12344
29. Hung, L. C.; Lin, C. C.; Hung, S. K.; Wu, B. C.; Jan, M. D.; Liou, S. H.; Fu, S. L. A synthetic analog of alpha-galactosylceramide induces macrophage activation via the TLR4-signaling pathways Biochem. Pharmacol. 2007, 73, 1957-1970
30. Huang, L. D.; Lin, H. J.; Huang, P. H.; Hsiao, W. C.; Reddy, L. V.; Fu, S. L.; Lin, C. C. Synthesis of serine-based glycolipids as potential TLR4 activators Org. Biomol. Chem. 2011, 9, 2492-2504
31. Lin, Y. S.; Huang, L. D.; Lin, C. H.; Huang, P. H.; Chen, Y. J.; Wong, F. H.; Lin, C. C.; Fu, S. L. In vitro and in vivo anticancer activity of a synthetic glycolipid as Toll-like receptor 4 (TLR4) activator J. Biol. Chem. 2011, 286, 43782-43792
32. Morita, M.; Motoki, K.; Akimoto, K.; Natori, T.; Sakai, T.; Sawa, E.; Yamaji, K.; Koezuka, Y.; Kobayashi, E.; Fukushima, H. Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice J. Med. Chem. 1995, 38, 2176-2187
33. Yamada, M.; Ichikawa, T.; Ii, M.; Sunamoto, M.; Itoh, K.; Tamura, N.; Kitazaki, T. Discovery of novel and potent small-molecule inhibitors of NO and cytokine production as antisepsis agents: synthesis and biological activity of alkyl 6-(N-substituted sulfamoyl)cyclohex-1-ene-1-carboxylate J. Med. Chem. 2005, 48, 7457-7467
34. Takashima, K.; Matsunaga, N.; Yoshimatsu, M.; Hazeki, K.; Kaisho, T.; Uekata, M.; Hazeki, O.; Akira, S.; Iizawa, Y.; Ii, M. Analysis of binding site for the novel small-molecule TLR4 signal transduction inhibitor TAK-242 and its therapeutic effect on mouse sepsis model Br. J. Pharmacol. 2009, 157, 1250-1262
35. Bevan, D. E.; Martinko, A. J.; Loram, L. C.; Stahl, J. A.; Taylor, F. R.; Joshee, S.; Watkins, L. R.; Yin, H. Selection, preparation, and evaluation of small-molecule inhibitors of Toll-like receptor 4 ACS Med. Chem. Lett. 2010, 1, 194-198
36. Chavez, S. A.; Martinko, A. J.; Lau, C.; Pham, M. N.; Cheng, K.; Bevan, D. E.; Mollnes, T. E.; Yin, H. Development of β-amino alcohol derivatives that inhibit Toll-like receptor 4 mediated inflammatory response as potential antiseptics J. Med. Chem. 2011, 54, 4659-4669
37. Chan, M.; Hayashi, T.; Mathewson, R. D.; Nour, A.; Hayashi, Y.; Yao, S.; Tawatao, R. I.; Crain, B.; Tsigelny, I. F.; Kouznetsova, V. L.; Messer, K.; Pu, M.; Corr, M.; Carson, D. A.; Cottam, H. B. Identification of substituted pyrimido[5,4- b ]indoles as selective Toll-like receptor 4 ligands J. Med. Chem. 2013, 56, 4206-4223
38. Slivka, P.; Shridhar, M.; Lee, G.; Sammond, D.; Hutchinson, M.; Martinko, A.; Buchanan, M.; Sholar, P.; Kearney, J.; Harrison, J.; Watkins, L.; Yin, H. A peptide antagonist of the TLR4.MD-2 interaction ChemBioChem 2009, 10, 645-649
39. Shanmugam, A.; Rajoria, S.; George, A. L.; Mittelman, A.; Suriano, R.; Tiwari, R. K. Synthetic Toll like receptor-4 (TLR-4) agonist peptides as a novel class of adjuvants PLoS One 2012, 7, e30839
40. Chahal, D. S.; Sivamani, R. K.; Rivkah Isseroff, R.; Dasu, M. R. Plant-based modulation of Toll-like receptors: an emerging therapeutic model Phytother. Res. 2013, 27, 1423-1438
41. Park, S. J.; Youn, H. S. Suppression of homodimerization of Toll-like receptor 4 by isoliquiritigenin Phytochemistry 2010, 71, 1736-1740
42. Ahn, S. I.; Lee, J. K.; Youn, H. S. Inhibition of homodimerization of Toll-like receptor 4 by 6-shogaol Mol. Cell 2009, 27, 211-215
43. Kim, S. Y.; Koo, J. E.; Seo, Y. J.; Tyagi, N.; Jeong, E.; Choi, J.; Lim, K. M.; Park, Z. Y.; Lee, J. Y. Suppression of Toll-like receptor 4 activation by caffeic acid phenethyl ester is mediated by interference of LPS binding to MD-2 Br. J. Pharmacol. 2013, 168, 1933-1945
44. Youn, H. S.; Lee, J. K.; Choi, Y. J.; Saitoh, S. I.; Miyake, K.; Hwang, D. H.; Lee, J. Y. Cinnamaldehyde suppresses Toll-like receptor 4 activation mediated through the inhibition of receptor oligomerization Biochem. Pharmacol. 2008, 75, 494-502
45. Gradisar, H.; Keber, M.; Pristovsek, P.; Jerala, R. MD-2 as the target of curcumin in the inhibition of response to LPS J. Leukocyte Biol. 2007, 82, 968-974
46. Youn, H. S.; Saitoh, S. I.; Miyake, K.; Hwang, D. H. Inhibition of homodimerization of Toll-like receptor 4 by curcumin Biochem. Pharmacol. 2006, 72, 62-69
47. Park, S. H.; Kyeong, M. S.; Hwang, Y.; Ryu, S. Y.; Han, S. B.; Kim, Y. Inhibition of LPS binding to MD-2 co-receptor for suppressing TLR4-mediated expression of inflammatory cytokine by 1-dehydro-10-gingerdione from dietary ginger Biochem. Biophys. Res. Commun. 2012, 419, 735-740
48. Koo, J. E.; Park, Z. Y.; Kim, N. D.; Lee, J. Y. Sulforaphane inhibits the engagement of LPS with TLR4/MD-2 complex by preferential binding to Cys133 in MD-2 Biochem. Biophys. Res. Commun. 2013, 434, 600-605
49. Park, S. J.; Lee, M. Y.; Son, B. S.; Youn, H. S. TBK1-targeted suppression of TRIF-dependent signaling pathway of Toll-like receptors by 6-shogaol, an active component of ginger Biosci., Biotechnol., Biochem. 2009, 73, 1474-1478
50. Kim, J. Y.; Park, S. J.; Yun, K. J.; Cho, Y. W.; Park, H. J.; Lee, K. T. Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-kappaB in RAW 264.7 macrophages Eur. J. Pharmacol. 2008, 584, 175-184
51. Schröfelbauer, B.; Raffetseder, J.; Hauner, M.; Wolkerstorfer, A.; Ernst, W.; Szolar, O. H. Glycyrrhizin, the main active compound in liquorice, attenuates pro-inflammatory responses by interfering with membrane-dependent receptor signaling Biochem. J. 2009, 421, 473-482
52. Honda, H.; Nagai, Y.; Matsunaga, T.; Saitoh, S.; Akashi-Takamura, S.; Hayashi, H.; Fujii, I.; Miyake, K.; Muraguchi, A.; Takatsu, K. Glycyrrhizin and isoliquiritigenin suppress the LPS sensor Toll-like receptor 4/MD-2 complex signaling in a different manner J. Leukocyte Biol. 2012, 91, 967-976
53. Natarajan, K.; Singh, S.; Burke, T. R.; Grunberger, D.; Aggarwal, B. B. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 9090-9095
54. Mapesa, J. O.; Waldschmitt, N.; Schmoeller, I.; Blume, C.; Hofmann, T.; Mahungu, S.; Clavel, T.; Haller, D. Catechols in caffeic acid phenethyl ester are essential for inhibition of TNF-mediated IP-10 expression through NF-κB-dependent but HO-1- and p38-independent mechanisms in mouse intestinal epithelial cells Mol. Nutr. Food Res. 2011, 55, 1850-1861
55. Youn, H. S.; Lee, J. Y.; Saitoh, S. I.; Miyake, K.; Kang, K. W.; Choi, Y. J.; Hwang, D. H. Suppression of MyD88- and TRIF-dependent signaling pathways of Toll-like receptor by (-)-epigallocatechin-3-gallate, a polyphenol component of green tea Biochem. Pharmacol. 2006, 72, 850-859
56. Resman, N.; Gradisar, H.; Vasl, J.; Keber, M.; Pristovsek, P.; Jerala, R. Taxanes inhibit human TLR4 signaling by binding to MD-2 FEBS Lett. 2008, 582, 3929-3934
57. Zhang, D.; Li, Y.; Liu, Y.; Xiang, X.; Dong, Z. Paclitaxel ameliorates lipopolysaccharide-induced kidney injury by binding myeloid differentiation protein-2 to block Toll-like receptor 4-mediated nuclear factor-κB activation and cytokine production J. Pharmacol. Exp. Ther. 2013, 345, 69-75
58. Zimmer, S. M.; Liu, J.; Clayton, J. L.; Stephens, D. S.; Snyder, J. P. Paclitaxel binding to human and murine MD-2 J. Biol. Chem. 2008, 283, 27916-27926
59. Wang, X.; Loram, L. C.; Ramos, K.; de Jesus, A. J.; Thomas, J.; Cheng, K.; Reddy, A.; Somogyi, A. A.; Hutchinson, M. R.; Watkins, L. R.; Yin, H. Morphine activates neuroinflammation in a manner parallel to endotoxin Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 6325-6330
60. Hutchinson, M. R.; Northcutt, A. L.; Hiranita, T.; Wang, X.; Lewis, S. S.; Thomas, J.; van Steeg, K.; Kopajtic, T. A.; Loram, L. C.; Sfregola, C.; Galer, E.; Miles, N. E.; Bland, S. T.; Amat, J.; Rozeske, R. R.; Maslanik, T.; Chapman, T. R.; Strand, K. A.; Fleshner, M.; Bachtell, R. K.; Somogyi, A. A.; Yin, H.; Katz, J. L.; Rice, K. C.; Maier, S. F.; Watkins, L. R. Opioid activation of Toll-like receptor 4 contributes to drug reinforcement J. Neurosci. 2012, 32, 11187-11200
61. Hutchinson, M. R.; Loram, L. C.; Zhang, Y.; Shridhar, M.; Rezvani, N.; Berkelhammer, D.; Phipps, S.; Foster, P. S.; Landgraf, K.; Falke, J. J.; Rice, K. C.; Maier, S. F.; Yin, H.; Watkins, L. R. Evidence that tricyclic small molecules may possess Toll-like receptor and myeloid differentiation protein 2 activity Neuroscience 2010, 168, 551-563
62. Hutchinson, M. R.; Zhang, Y.; Brown, K.; Coats, B. D.; Shridhar, M.; Sholar, P. W.; Patel, S. J.; Crysdale, N. Y.; Harrison, J. A.; Maier, S. F.; Rice, K. C.; Watkins, L. R. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of Toll-like receptor 4 (TLR4) Eur. J. Neurosci. 2008, 28, 20-29
63. Lewis, S. S.; Loram, L. C.; Hutchinson, M. R.; Li, C. M.; Zhang, Y.; Maier, S. F.; Huang, Y.; Rice, K. C.; Watkins, L. R. (+)-Naloxone, an opioid-inactive Toll-like receptor 4 signaling inhibitor, reverses multiple models of chronic neuropathic pain in rats J. Pain 2012, 13, 498-506
64. Panda, S. K.; Kumar, S.; Tupperwar, N. C.; Vaidya, T.; George, A.; Rath, S.; Bal, V.; Ravindran, B. Chitohexaose activates macrophages by alternate pathway through TLR4 and blocks endotoxemia PLoS Pathog. 2012, 8, e1002717
65. Ariza, M. E.; Ramakrishnan, R.; Singh, N. P.; Chauhan, A.; Nagarkatti, P. S.; Nagarkatti, M. Bryostatin-1, a naturally occurring antineoplastic agent, acts as a Toll-like receptor 4 (TLR-4) ligand and induces unique cytokines and chemokines in dendritic cells J. Biol. Chem. 2011, 286, 24-34
66. Xu, Y.; Wang, G.; Li, C.; Zhang, M.; Zhao, H.; Sheng, J.; Shi, W. Pu-erh tea reduces nitric oxide levels in rats by inhibiting inducible nitric oxide synthase expression through Toll-like receptor 4 Int. J. Mol. Sci. 2012, 13, 7174-7185
67. Fang, H. L.; Lai, J. T.; Lin, W. C. Inhibitory effect of olive oil on fibrosis induced by carbon tetrachloride in rat liver Clin. Nutr. 2008, 27, 900-907
68. Barochia, A.; Solomon, S.; Cui, X.; Natanson, C.; Eichacker, P. Q. Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies Expert Opin. Drug Metab. Toxicol. 2011, 7, 479-494
69. Martins, P. S.; Brunialti, M. K.; Martos, L. S.; Machado, F. R.; Assuncao, M. S.; Blecher, S.; Salomao, R. Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis Crit. Care 2008, 12, R25
70. Kayagaki, N.; Wong, M. T.; Stowe, I. B.; Ramani, S. R.; Gonzalez, L. C.; Akashi-Takamura, S.; Miyake, K.; Zhang, J.; Lee, W. P.; Muszyński, A.; Forsberg, L. S.; Carlson, R. W.; Dixit, V. M. Noncanonical inflammasome activation by intracellular LPS independent of TLR4 Science 2013, 341, 1246-1249