Multifunctional role of dextran sulfate sodium for <it>in vivo</it> modeling of intestinal diseases
<p>Abstract</p> <p>Background</p> <p>Inflammatory bowel diseases (IBDs) are chronic, relapsing disorders that affect the gastrointestinal tract of millions of people and continue to increase in incidence each year. While several factors have been associated with develop...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-08-01
|
| Series: | BMC Immunology |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1471-2172/13/41 |
| _version_ | 1811314861107314688 |
|---|---|
| author | Rose William A Sakamoto Kaori Leifer Cynthia A |
| author_facet | Rose William A Sakamoto Kaori Leifer Cynthia A |
| author_sort | Rose William A |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inflammatory bowel diseases (IBDs) are chronic, relapsing disorders that affect the gastrointestinal tract of millions of people and continue to increase in incidence each year. While several factors have been associated with development of IBDs, the exact etiology is unknown. Research using animal models of IBDs is beginning to provide insights into how the different factors contribute to disease development. Oral administration of dextran sulfate sodium (DSS) to mice induces a reproducible experimental colitis that models several intestinal lesions associated with IBDs. The murine DSS colitis model can also be adapted to quantify intestinal repair following injury. Understanding the mechanistic basis behind intestinal repair is critical to development of new therapeutics for IBDs because of their chronic relapsing nature.</p> <p>Results</p> <p>The murine DSS colitis model was adapted to provide a system enabling the quantification of severe intestinal injury with impaired wound healing or mild intestinal injury with rapid restoration of mucosal integrity, by altering DSS concentrations and including a recovery phase. We showed that through a novel format for presentation of the clinical disease data, the temporal progression of intestinal lesions can be quantified on an individual mouse basis. Additionally, parameters for quantification of DSS-induced alterations in epithelial cell populations are included to provide insights into mechanisms underlying the development of these lesions. For example, the use of the two different model systems showed that toll-like receptor 9, a nucleic acid-sensing pattern recognition receptor, is important for protection only following mild intestinal damage and suggests that this model is superior for identifying proteins necessary for intestinal repair.</p> <p>Conclusions</p> <p>We showed that using a murine DSS-induced experimental colitis model system, and presenting data in a longitudinal manner on a per mouse basis, enhanced the usefulness of this model, and provided novel insights into the role of an innate immune receptor in intestinal repair. By elucidating the mechanistic basis of intestinal injury and repair, we can begin to understand the etiology of IBDs, enabling development of novel therapeutics or prophylactics.</p> |
| first_indexed | 2024-04-13T11:19:57Z |
| format | Article |
| id | doaj.art-798a6577f41440bba5ef40418263d947 |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-04-13T11:19:57Z |
| publishDate | 2012-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-798a6577f41440bba5ef40418263d9472022-12-22T02:48:51ZengBMCBMC Immunology1471-21722012-08-011314110.1186/1471-2172-13-41Multifunctional role of dextran sulfate sodium for <it>in vivo</it> modeling of intestinal diseasesRose William ASakamoto KaoriLeifer Cynthia A<p>Abstract</p> <p>Background</p> <p>Inflammatory bowel diseases (IBDs) are chronic, relapsing disorders that affect the gastrointestinal tract of millions of people and continue to increase in incidence each year. While several factors have been associated with development of IBDs, the exact etiology is unknown. Research using animal models of IBDs is beginning to provide insights into how the different factors contribute to disease development. Oral administration of dextran sulfate sodium (DSS) to mice induces a reproducible experimental colitis that models several intestinal lesions associated with IBDs. The murine DSS colitis model can also be adapted to quantify intestinal repair following injury. Understanding the mechanistic basis behind intestinal repair is critical to development of new therapeutics for IBDs because of their chronic relapsing nature.</p> <p>Results</p> <p>The murine DSS colitis model was adapted to provide a system enabling the quantification of severe intestinal injury with impaired wound healing or mild intestinal injury with rapid restoration of mucosal integrity, by altering DSS concentrations and including a recovery phase. We showed that through a novel format for presentation of the clinical disease data, the temporal progression of intestinal lesions can be quantified on an individual mouse basis. Additionally, parameters for quantification of DSS-induced alterations in epithelial cell populations are included to provide insights into mechanisms underlying the development of these lesions. For example, the use of the two different model systems showed that toll-like receptor 9, a nucleic acid-sensing pattern recognition receptor, is important for protection only following mild intestinal damage and suggests that this model is superior for identifying proteins necessary for intestinal repair.</p> <p>Conclusions</p> <p>We showed that using a murine DSS-induced experimental colitis model system, and presenting data in a longitudinal manner on a per mouse basis, enhanced the usefulness of this model, and provided novel insights into the role of an innate immune receptor in intestinal repair. By elucidating the mechanistic basis of intestinal injury and repair, we can begin to understand the etiology of IBDs, enabling development of novel therapeutics or prophylactics.</p>http://www.biomedcentral.com/1471-2172/13/41Dextran sulfate sodiumInflammatory bowel diseaseIntestinal repairToll-like receptor 9 |
| spellingShingle | Rose William A Sakamoto Kaori Leifer Cynthia A Multifunctional role of dextran sulfate sodium for <it>in vivo</it> modeling of intestinal diseases BMC Immunology Dextran sulfate sodium Inflammatory bowel disease Intestinal repair Toll-like receptor 9 |
| title | Multifunctional role of dextran sulfate sodium for <it>in vivo</it> modeling of intestinal diseases |
| title_full | Multifunctional role of dextran sulfate sodium for <it>in vivo</it> modeling of intestinal diseases |
| title_fullStr | Multifunctional role of dextran sulfate sodium for <it>in vivo</it> modeling of intestinal diseases |
| title_full_unstemmed | Multifunctional role of dextran sulfate sodium for <it>in vivo</it> modeling of intestinal diseases |
| title_short | Multifunctional role of dextran sulfate sodium for <it>in vivo</it> modeling of intestinal diseases |
| title_sort | multifunctional role of dextran sulfate sodium for it in vivo it modeling of intestinal diseases |
| topic | Dextran sulfate sodium Inflammatory bowel disease Intestinal repair Toll-like receptor 9 |
| url | http://www.biomedcentral.com/1471-2172/13/41 |
| work_keys_str_mv | AT rosewilliama multifunctionalroleofdextransulfatesodiumforitinvivoitmodelingofintestinaldiseases AT sakamotokaori multifunctionalroleofdextransulfatesodiumforitinvivoitmodelingofintestinaldiseases AT leifercynthiaa multifunctionalroleofdextransulfatesodiumforitinvivoitmodelingofintestinaldiseases |