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A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease
Abstract
Current evidence indicates that the chronic inflammation observed in the intestines of patients with inflammatory bowel disease is due to an aberrant immune response to enteric flora. We have developed a lipid A-mimetic, CRX-526, which has antagonistic activity for TLR4 and can block the interaction of LPS with the immune system. CRX-526 can prevent the expression of proinflammatory genes stimulated by LPS in vitro. This antagonist activity of CRX-526 is directly related to its structure, particularly secondary fatty acyl chain length. In vivo, CRX-526 treatment blocks the ability of LPS to induce TNF-alpha release. Importantly, treatment with CRX-526 inhibits the development of moderate-to-severe disease in two mouse models of colonic inflammation: the dextran sodium sulfate model and multidrug resistance gene 1a-deficient mice. By blocking the interaction between enteric bacteria and the innate immune system, CRX-526 may be an effective therapeutic molecule for inflammatory bowel disease.
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“Importantly, treatment with a TLR4 antagonist (CRX-526) inhibited the development of disease in an acute DSS colitis model.108”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [108]
Citations
Cites
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Hugot, J.-P., Chamaillard, M., Zouali, H., Lesage, S., Cézard, J.-P., Belaiche, J., Almer, S., Tysk, C., O'Morain, C. A., Gassull, M., et al. (2001) · Nature · doi:10.1038/35079107 · Cited by 5,591
A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
Ogura, Y., Bonen, D. K., Inohara, N., Nicolae, D. L., Chen, F. F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerr, R. H., et al. (2001) · Nature · doi:10.1038/35079114 · Cited by 5,030
Toll-like receptors: critical proteins linking innate and acquired immunity
Akira, S., Takeda, K., & Kaisho, T. (2001) · Nature Immunology · doi:10.1038/90609 · Cited by 4,777
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251
Clinicopathologic study of dextran sulfate sodium experimental acute colitis
Shichijo, K., Matuu, M., Ikeda, Y., Naito, S., Ito, M., & Sekine, I. (1998) · The Japanese Journal of Pharmacology · doi:10.1016/s0021-5198(19)41298-5 · Cited by 1,945
The Immunology of Mucosal Models of Inflammation
Strober, W., Fuss, I. J., & Blumberg, R. S. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064816 · Cited by 1,300
Cario, E., & Podolsky, D. K. (2000) · Infection and Immunity · doi:10.1128/iai.68.12.7010-7017.2000 · Cited by 1,245
Takeda, K., Clausen, B. E., Kaisho, T., Tsujimura, T., Terada, N., Förster, I., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80005-9 · Cited by 1,220
Duchmann, R., Kaiser, I., Hermann, E., Mayet, W.-J., Ewe, K., & BÜSCHENFELDE, K.-H. M. Z. (1995) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1995.tb03836.x · Cited by 938
Abreu, M. T., Vora, P., Faure, E., Thomas, L. S., Arnold, E. T., & Arditi, M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1609 · Cited by 681
Panwala, C. M., Jones, J. C., & Viney, J. L. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.10.5733 · Cited by 567
Recognition of microbial infection by Toll-like receptors
Kopp, E. B., & Medzhitov, R. M. (2003) · Current Opinion in Immunology · doi:10.1016/s0952-7915(03)00080-3 · Cited by 553
Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation
Hausmann, M., Kießling, S., Mestermann, S., Webb, G. R., Spöttl, T., Andus, T., Schölmerich, J., Herfarth, H. H., Ray, K., Falk, W., et al. (2002) · Gastroenterology · doi:10.1053/gast.2002.33662 · Cited by 488
Poltorak, A. N., Ricciardi‐Castagnoli, P., Citterio, S., & Beutler, B. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040565397 · Cited by 430
Lipopolysaccharide Interaction with Cell Surface Toll-like Receptor 4-MD-2
Akashi, S., Saitoh, S.-I., Wakabayashi, Y., Kikuchi, T., Takamura, N., Nagai, Y., Kusumoto, Y., Fukase, K., Kusumoto, S., Adachi, Y., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20031076 · Cited by 385
Biologic therapy of inflammatory bowel disease
Sandborn, W. J., & Targan, S. R. (2002) · Gastroenterology · doi:10.1053/gast.2002.33426 · Cited by 341
Hornef, M. W., Normark, B. H., Vandewalle, A., & Normark, S. J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022194 · Cited by 330
Smith, P. D., Smythies, L. E., Mosteller‐Barnum, M., Sibley, D. A., Russell, M. W., Merger, M., Sellers, M. T., Orenstein, J. M., Shimada, T., Graham, M. F., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.5.2651 · Cited by 327
Control of adaptive immune responses by Toll-like receptors
Barton, G. M., & Medzhitov, R. M. (2002) · Current Opinion in Immunology · doi:10.1016/s0952-7915(02)00343-6 · Cited by 327
Means, T. K., Jones, B. W., Schromm, A. B., Shurtleff, B. A., Smith, J. A., Keane, J., Golenbock, D. T., Vogel, S. N., & Fenton, M. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.6.4074 · Cited by 269
MD-2 and TLR4 N-Linked Glycosylations Are Important for a Functional Lipopolysaccharide Receptor
Correia, J. D. S., & Ulevitch, R. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109910200 · Cited by 262
Taking toll: lipid A mimetics as adjuvants and immunomodulators
Persing, D. H., Coler, R. N., Lacy, M. J., Johnson, D. A., Baldridge, J. R., Hershberg, R. M., & Reed, S. G. (2002) · Trends in Microbiology · doi:10.1016/s0966-842x(02)02426-5 · Cited by 260
Kobayashi, M., Kweon, M., Kuwata, H., Schreiber, R. D., Kiyono, H., Takeda, K., & Akira, S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17085 · Cited by 251
Therapy of inflammatory bowel disease
Sands, B. E. (2000) · Gastroenterology · doi:10.1016/s0016-5085(00)70007-2 · Cited by 235
Structure-Activity Relationship of Synthetic Toll-like Receptor 4 Agonists
Stöver, A. G., Correia, J. D. S., Evans, J. T., Cluff, C. W., Elliott, M. W., Jeffery, E. W., Johnson, D. A., Lacy, M. J., Baldridge, J. R., Probst, P., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310760200 · Cited by 159
Activation of Mammalian Toll-like Receptors by Endogenous Agonists
Johnson, G. B., Brunn, G. J., & Platt, J. L. (2003) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v23.i12.20 · Cited by 143
Maggio‐Price, L., Shows, D. M., Waggie, K. S., Burich, A., Zeng, W., Escobar, S. M., Morrissey, P., & Viney, J. L. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64894-8 · Cited by 135
Autoimmunity and Apoptosis: The Crohn's Connection
Beutler, B. (2001) · Immunity · doi:10.1016/s1074-7613(01)00176-5 · Cited by 118
Probst, P., Skeiky, Y. A. W., Steeves, M., Gervassi, A. L., Grabstein, K. H., & Reed, S. G. (1997) · European Journal of Immunology · doi:10.1002/eji.1830271024 · Cited by 96
Responses to self and non-self intestinal microflora in health and inflammatory bowel disease
Duchmann, R., Neurath, M. F., & Büschenfelde, K. H. M. Z. (1997) · Research in Immunology · doi:10.1016/s0923-2494(98)80154-5 · Cited by 87
Johnson, D. A., Sowell, C. G., Johnson, C. L., Livesay, M. T., Keegan, D. S., Rhodes, M. J., Ulrich, J. T., Ward, J. R., Cantrell, J. L., & Brookshire, V. G. (1999) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(99)00374-1 · Cited by 67
Kawata, T., Bristol, J. R., Rossignol, D. P., Rose, J., Kobayashi, S., Yokohama, H., Ishibashi, A., Christ, W. J., Katayama, K., Yamatsu, I., et al. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702596 · Cited by 62
Probiotics in inflamatory bowel disease
Shanahan, F. (2001) · Gut · doi:10.1136/gut.48.5.609 · Cited by 60
The role of the Lps gene in experimental ulcerative colitis in mice
Lange, S., Delbro, D. S., Jennische, E., & Mattsby‐Baltzer, I. (1996) · Apmis · doi:10.1111/j.1699-0463.1996.tb04948.x · Cited by 46
The C3H/HeJBir Mouse Model: A High Susceptibility Phenotype for Colitis
Elson, C. O., Cong, Y., & Sundberg, J. P. (2000) · International Reviews of Immunology · doi:10.3109/08830180009048390 · Cited by 34
Baker, P. J., Hrabă, T., Taylor, C. E., Myers, K. R., Takayama, K., Qureshi, N., Stuetz, P. L., Kusumoto, S., & Hasegawa, A. (1992) · Infection and Immunity · doi:10.1128/iai.60.7.2694-2701.1992 · Cited by 26
Research works printed but not linked: 38
- 2000, Gastroenterology, S68
- 2002, Gastroenterology, 1592
- 1995, Clin. Exp. Immunol., 448
- 1997, Res. Immunol., 589
- 2001, Immunity, 5
- 2001, Nature, 603
- 2001, Nature, 599
- 2001, Gut, 609
- 2002, Annu. Rev. Immunol., 495
- 2002, Annu. Rev. Immunol., 197
- 2003, Annu. Rev. Immunol., 335
- 2003, Curr. Opin. Immunol., 396
- 2000, Proc. Natl. Acad. Sci. USA, 2163
- 2002, J. Biol. Chem., 1845
- 2003, J. Exp. Med., 1035
- 2001, Nat. Immunol., 675
- 2002, Curr. Opin. Immunol., 380
- 2003, Crit. Rev. Immunol., 15
- 1999, Bioorg. Med. Chem. Lett., 2273
- 2002, Trends Microbiol., S32
- 1992, Infect. Immun., 2694
- 2003, J. Biol. Chem., 4440
- 1997, Eur. J. Immunol., 2634
- 1993, Lab. Invest., 238
- 2002, Am. J. Pathol., 739
- 1996, APMIS, 823
- 1998, J. Immunol., 5733
- 2000, Int. Rev. Immunol., 63
- 1999, Immunity, 39
- 2003, J. Clin. Invest., 1297
- 2004, Cell, 229
- 2001, J. Immunol., 1609
- 1999, Br. J. Pharmacol., 853
- 2001, J. Immunol., 4074
- 2001, J. Immunol., 2651
- 2003, J. Exp. Med., 1225
- 2000, Infect. Immun., 7010
- 2002, Gastroenterology, 1987
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Abreu, M. T. (2010) · Nature Reviews Immunology · doi:10.1038/nri2707 · Cited by 1,288
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Metadata
- Authors
- Fort, M. M., Mozaffarian, A., Stöver, A. G., Correia, J. D. S., Johnson, D. A., Crane, R. T., Ulevitch, R. J., Persing, D. H., Bielefeldt-Ohmann, H., Probst, P., Jeffery, E., Fling, S. P., & Hershberg, R. M.
- Affiliations
- Scripps Research Institute (US)
- Corixa Corporation , Seattle, WA 98101
- Washington National Primate Research Center, University of Washington , Seattle, WA 98195
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-05
- Volume
- 174
- Issue
- 10
- Pages
- 6416-6423
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1906569767
- Cited by
- 216
- References
- 38
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 13 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 5 · 2014: 12 · 2013: 15 · 2012: 10
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- TLR4 antagonist, inflammatory bowel disease, lipopolysaccharide, TNF-α, DSS-induced colitis, innate immunity, enteric bacteria, anti-inflammatory therapy, acyl chain length
- MeSH terms
- Adjuvants, Immunologic, Animals, Anti-Inflammatory Agents, Non-Steroidal, Caproates, Cells, Cultured, Colitis, Disease Models, Animal, Female, Glucosamine, HeLa Cells, Humans, Lipid A, Lipopolysaccharides, Mice, Inbred BALB C, Mice, Inbred C3H, Monocytes, Receptors, Immunologic, Tumor Necrosis Factor-alpha, Inflammatory Bowel Diseases, Dextran Sulfate, Mice, Knockout, ATP Binding Cassette Transporter, Subfamily B, Member 1, Toll-Like Receptor 4, Mice
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