Journal article
5-Lipoxygenase-derived lipid mediators are not required for the development of NSAID-induced inflammatory bowel disease in IL-10-/- mice
American journal of physiology: Gastrointestinal and liver physiology, Vol.294(2), pp.G477-488
02/2008
DOI: 10.1152/ajpgi.00229.2007
PMID: 18048478
Abstract
Leukotrienes are potent lipid mediators derived from the metabolism of arachidonic acid by the enzyme 5-lipoxygenase (5-LO). Elevated levels of the proinflammatory leukotriene LTB(4) have been found in preclinical models of inflammatory bowel disease (IBD) as well as in colon tissue from individuals with IBD. We therefore determined the extent to which absence of 5-LO-derived lipid mediators would alter the colitis in IL-10(-/-) mice, a model of human IBD. IL-10(-/-)/5-LO(-/-) mice were generated and were healthy. Absence of 5-LO did not alter the development of spontaneous colitis in IL-10-deficient mice. We then evaluated the extent to which absence of 5-LO would alter the development of NSAID-induced colitis in IL-10(-/-) mice. Absence of 5-LO did not delay the onset or alter the severity of inflammation in NSAID-treated IL-10(-/-) mice. At an early time point, 3 days after NSAID treatment was initiated, a qualitative increase in the number of dendritic cells and CD4(+) T cells was noted in the colons of IL-10(-/-)/5-LO(-/-); however, this difference was no longer present after 14 days of NSAID treatment. Absence of 5-LO did not alter the degree of neutrophil infiltration into the in this model. Absence of 5-LO does not alter the development of IFN-gamma producing Th1-type CD4(+) T cells or IL-17 producing CD4(+) T cells. Absence of 5-LO-derived mediators did not alter the expression of the adhesion molecules ICAM-1 and P-selectin. Development of colitis in IL-10(-/-) mice was associated with increased levels of the 5-LO-derived anti-inflammatory lipoxin LXA(4). These studies demonstrate that 5-LO-derived leukotrienes are not required for the development or maintenance of spontaneous or NSAID-induced colonic inflammation in IL-10(-/-) mice.
Details
- Title: Subtitle
- 5-Lipoxygenase-derived lipid mediators are not required for the development of NSAID-induced inflammatory bowel disease in IL-10-/- mice
- Creators
- Seiko Narushima - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USADaniel DiMeoJun TianJuan ZhangDahzi LiuDaniel J Berg
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: Gastrointestinal and liver physiology, Vol.294(2), pp.G477-488
- DOI
- 10.1152/ajpgi.00229.2007
- PMID
- 18048478
- ISSN
- 0193-1857
- eISSN
- 1522-1547
- Grant note
- R01 DK-060718-01A2 / NIDDK NIH HHS
- Language
- English
- Date published
- 02/2008
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094550402771
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