Cited by 217Immune Response and InflammationInflammatory Bowel DiseasePsoriasis: Treatment and Pathogenesis

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A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease

Fort, Madeline M, Mozaffarian, Afsaneh, Stöver, Axel G, Correia, Jean da Silva, Johnson, David A, Crane, R Thomas, Ulevitch, Richard J, Persing, David H, Bielefeldt-Ohmann, Helle, Probst, Peter, Jeffery, Eric, Fling, Steven P, Hershberg, Robert M·2005·The Journal of Immunology

DOI 10.4049/jimmunol.174.10.6416

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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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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
ORCID: Fort, Madeline M
Johnson, David A
Ulevitch, Richard J
Fling, Steven P
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
DOI: 10.4049/jimmunol.174.10.6416
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
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
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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A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease

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