Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine
Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tu...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/852378 |
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| _version_ | 1832563818059792384 |
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| author | Kathryn S. Brown Huiyu Gong Mark R. Frey Brock Pope Matthew Golden Katerina Martin Mitchel Obey Steven J. McElroy |
| author_facet | Kathryn S. Brown Huiyu Gong Mark R. Frey Brock Pope Matthew Golden Katerina Martin Mitchel Obey Steven J. McElroy |
| author_sort | Kathryn S. Brown |
| collection | DOAJ |
| description | Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF) has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1) mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC. |
| format | Article |
| id | doaj-art-0020bb3defff47f5b6f45e4d9de92b21 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-0020bb3defff47f5b6f45e4d9de92b212025-02-03T01:12:28ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/852378852378Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small IntestineKathryn S. Brown0Huiyu Gong1Mark R. Frey2Brock Pope3Matthew Golden4Katerina Martin5Mitchel Obey6Steven J. McElroy7Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USADepartment of Pediatrics, University of Iowa, Iowa City, IA 52242, USADepartments of Pediatrics and Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine and The Saban Research Institute at Children’s Hospital Los Angeles, Los Angeles, CA 90027, USADepartment of Pediatrics, University of Iowa, Iowa City, IA 52242, USADepartment of Pediatrics, University of Iowa, Iowa City, IA 52242, USADepartment of Pediatrics, University of Iowa, Iowa City, IA 52242, USADepartment of Pediatrics, University of Iowa, Iowa City, IA 52242, USADepartment of Pediatrics, University of Iowa, Iowa City, IA 52242, USABackground. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF) has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1) mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC.http://dx.doi.org/10.1155/2014/852378 |
| spellingShingle | Kathryn S. Brown Huiyu Gong Mark R. Frey Brock Pope Matthew Golden Katerina Martin Mitchel Obey Steven J. McElroy Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine Mediators of Inflammation |
| title | Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine |
| title_full | Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine |
| title_fullStr | Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine |
| title_full_unstemmed | Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine |
| title_short | Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine |
| title_sort | tumor necrosis factor induces developmental stage dependent structural changes in the immature small intestine |
| url | http://dx.doi.org/10.1155/2014/852378 |
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