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A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease
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| Zeitschriftentitel: | The Journal of Immunology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , |
| In: | The Journal of Immunology, 174, 2005, 10, S. 6416-6423 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The American Association of Immunologists
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| Schlagwörter: |
| author_facet |
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. 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. |
|---|---|
| author |
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. |
| spellingShingle |
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. The Journal of Immunology A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease Immunology Immunology and Allergy |
| author_sort |
fort, madeline m. |
| spelling |
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. 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.174.10.6416 <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> A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease The Journal of Immunology |
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| title |
A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_unstemmed |
A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_full |
A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_fullStr |
A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_full_unstemmed |
A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_short |
A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_sort |
a synthetic tlr4 antagonist has anti-inflammatory effects in two murine models of inflammatory bowel disease |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.4049/jimmunol.174.10.6416 |
| publishDate |
2005 |
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6416-6423 |
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<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> |
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| author | 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. |
| author_facet | 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., 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. |
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| description | <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> |
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| spelling | 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. 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.174.10.6416 <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> A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease The Journal of Immunology |
| spellingShingle | 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., The Journal of Immunology, A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease, Immunology, Immunology and Allergy |
| title | A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_full | A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_fullStr | A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_full_unstemmed | A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_short | A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| title_sort | a synthetic tlr4 antagonist has anti-inflammatory effects in two murine models of inflammatory bowel disease |
| title_unstemmed | A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.4049/jimmunol.174.10.6416 |