Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: Impact of a “Top‐Down” approach to intestinal fibrosis in mice
dc.contributor.author | Johnson, Laura A. | en_US |
dc.contributor.author | Luke, Amy | en_US |
dc.contributor.author | Sauder, Kay L. | en_US |
dc.contributor.author | Moons, David S. | en_US |
dc.contributor.author | Horowitz, Jeffrey C. | en_US |
dc.contributor.author | Higgins, Peter D.R. | en_US |
dc.date.accessioned | 2012-03-16T16:00:57Z | |
dc.date.available | 2013-05-01T17:24:43Z | en_US |
dc.date.issued | 2012-03 | en_US |
dc.identifier.citation | Johnson, Laura A.; Luke, Amy; Sauder, Kay; Moons, David S.; Horowitz, Jeffrey C.; Higgins, Peter D.R. (2012). "Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: Impact of a “Top‐Down” approach to intestinal fibrosis in mice ." Inflammatory Bowel Diseases 18(3): 460-471. <http://hdl.handle.net/2027.42/90367> | en_US |
dc.identifier.issn | 1078-0998 | en_US |
dc.identifier.issn | 1536-4844 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/90367 | |
dc.description.abstract | Background: The natural history of Crohn's disease follows a path of progression from an inflammatory to a fibrostenosing disease, with most patients requiring surgical resection of fibrotic strictures. Potent antiinflammatory therapies reduce inflammation but do not appear to alter the natural history of intestinal fibrosis. The aim of this study was to determine the relationship between intestinal inflammation and fibrogenesis and the impact of a very early “top‐down” interventional approach on fibrosis in vivo. Methods: In this study we removed the inflammatory stimulus from the Salmonella typhimurium mouse model of intestinal fibrosis by eradicating the S. typhimurium infection with levofloxacin at sequential timepoints during the infection. We evaluated the effect of this elimination of the inflammatory stimulus on the natural history of inflammation and fibrosis as determined by gross pathology, histopathology, mRNA expression, and protein expression. Results: Fibrogenesis is preceded by inflammation. Delayed eradication of the inflammatory stimulus by antibiotic treatment represses inflammation without preventing fibrosis. Early intervention significantly ameliorates but does not completely prevent subsequent fibrosis. Conclusions: This study demonstrates that intestinal fibrosis develops despite removal of an inflammatory stimulus and elimination of inflammation. Early intervention ameliorates but does not abolish subsequent fibrosis, suggesting that fibrosis, once initiated, is self‐propagating, suggesting that a very early top‐down interventional approach may have the most impact on fibrostenosing disease. (Inflamm Bowel Dis 2012;) | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Salmonella Typhimurium | en_US |
dc.subject.other | Crohn's Disease | en_US |
dc.subject.other | Intestinal Fibrosis | en_US |
dc.subject.other | Colitis | en_US |
dc.subject.other | Top‐Down Interventional Approach | en_US |
dc.title | Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: Impact of a “Top‐Down” approach to intestinal fibrosis in mice | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Hospitals, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Hospitals, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan Hospitals, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | SPC 5682, 1150 West Medical Center Dr., Ann Arbor, MI 48109 | en_US |
dc.identifier.pmid | 21761511 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/90367/1/21812_ftp.pdf | |
dc.identifier.doi | 10.1002/ibd.21812 | en_US |
dc.identifier.source | Inflammatory Bowel Diseases | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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