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

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Bibliographische Detailangaben
Zeitschriftentitel:	The Journal of Immunology
Personen und Körperschaften:	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.
In:	The Journal of Immunology, 174, 2005, 10, S. 6416-6423
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	The American Association of Immunologists
Schlagwörter:	Immunology Immunology and Allergy

Details
Zusammenfassung:	<jats:title>Abstract</jats:title> <jats:p>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-α 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.</jats:p>
Umfang:	6416-6423
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.174.10.6416