期刊
PLOS ONE
卷 4, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0004562
关键词
-
资金
- NIH [ROI DK 47700, P30 DK034987]
- American Institute of Cancer Research
Background: The impact of tomato lycopene extract (TLE) on intestinal inflammation is currently unknown. We investigated the effect of TLE on lipopolysaccharide (LPS)-induced innate signaling and experimental colitis. Methodology/Principal Findings: Mice were fed a diet containing 0.5 and 2% TLE or isoflavone free control (AIN-76). The therapeutic efficacy of TLE diet was assessed using dextran sulfate sodium (DSS) exposed mice and IL-10(-/-); NF-kappa B-EGFP mice, representing an acute and spontaneous chronic colitis model respectively. A mini-endoscope was used to determine the extent of macroscopic mucosal lesions. Murine splenocytes and intestinal epithelial cells were used to determine the in vitro impact of TLE on LPS-induced NF-kappa B signaling. In vitro, TLE blocked LPS-induced IkB alpha degradation, RelA translocation, NFkB transcriptional activity and MIP-2 mRNA accumulation in IEC-18 cells. Moreover, LPS-induced IL-12p40 gene expression was dose-dependently inhibited in TLE-treated splenocytes. Interestingly, DSS-induced acute colitis worsened in TLE-fed NF-kappa B-EGFP mice compared to control diet as measured by weight loss, colonoscopic analysis and histological scores. In contrast, TLE-fed IL-10(-/-); NF-kappa B-EGFP mice displayed decreased colonic EGFP expression compared to control diet. IL-6, TNF alpha, and MCP-1 mRNA expression were increased in the colon of TLE-fed, DSS-exposed NF-kappa B-EGFP mice compared to the control diet. Additionally, caspase-3 activation and TUNEL positive cells were enhanced in TLE diet-fed, DSS-exposed mice as compared to DSS control mice. Conclusions/Significance: These results indicate that TLE prevents LPS-induced proinflammatory gene expression by blocking of NF-kappa B signaling, but aggravates DSS-induced colitis by enhancing epithelial cell apoptosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据