CCR9 Antagonists in the Treatment of Ulcerative Colitis
While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward t...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/628340 |
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| _version_ | 1832551424927465472 |
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| author | Pirow Bekker Karen Ebsworth Matthew J. Walters Robert D. Berahovich Linda S. Ertl Trevor T. Charvat Sreenivas Punna Jay P. Powers James J. Campbell Timothy J. Sullivan Juan C. Jaen Thomas J. Schall |
| author_facet | Pirow Bekker Karen Ebsworth Matthew J. Walters Robert D. Berahovich Linda S. Ertl Trevor T. Charvat Sreenivas Punna Jay P. Powers James J. Campbell Timothy J. Sullivan Juan C. Jaen Thomas J. Schall |
| author_sort | Pirow Bekker |
| collection | DOAJ |
| description | While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a−/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a−/− mice. In the mdr1a−/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation. |
| format | Article |
| id | doaj-art-c638bdfdaf0d453fa06dafe9158d5f09 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-c638bdfdaf0d453fa06dafe9158d5f092025-02-03T06:01:35ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/628340628340CCR9 Antagonists in the Treatment of Ulcerative ColitisPirow Bekker0Karen Ebsworth1Matthew J. Walters2Robert D. Berahovich3Linda S. Ertl4Trevor T. Charvat5Sreenivas Punna6Jay P. Powers7James J. Campbell8Timothy J. Sullivan9Juan C. Jaen10Thomas J. Schall11ChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USAWhile it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a−/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a−/− mice. In the mdr1a−/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation.http://dx.doi.org/10.1155/2015/628340 |
| spellingShingle | Pirow Bekker Karen Ebsworth Matthew J. Walters Robert D. Berahovich Linda S. Ertl Trevor T. Charvat Sreenivas Punna Jay P. Powers James J. Campbell Timothy J. Sullivan Juan C. Jaen Thomas J. Schall CCR9 Antagonists in the Treatment of Ulcerative Colitis Mediators of Inflammation |
| title | CCR9 Antagonists in the Treatment of Ulcerative Colitis |
| title_full | CCR9 Antagonists in the Treatment of Ulcerative Colitis |
| title_fullStr | CCR9 Antagonists in the Treatment of Ulcerative Colitis |
| title_full_unstemmed | CCR9 Antagonists in the Treatment of Ulcerative Colitis |
| title_short | CCR9 Antagonists in the Treatment of Ulcerative Colitis |
| title_sort | ccr9 antagonists in the treatment of ulcerative colitis |
| url | http://dx.doi.org/10.1155/2015/628340 |
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