Tomato lycopene extract prevents lipopolysaccharide-induced NF-kappaB signaling but worsens dextran sulfate sodium-induced colitis in NF-kappaBEGFP mice.
Tomato lycopene extract prevents lipopolysaccharide-induced NF-kappaB signaling but worsens dextran sulfate sodium-induced colitis in NF-kappaBEGFP mice.
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DOI：
10.1371/journal.pone.0004562
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Jobin C
中科院分区：
文献类型：
--
作者：
Joo YE;Karrasch T;Mühlbauer M;Allard B;Narula A;Herfarth HH;Jobin C
番茄番茄红素提取物（TLE）对肠道炎症的影响目前尚不清楚。我们研究了TLE对脂多糖（LPS）诱导的先天性信号传导和实验性结肠炎的影响。给小鼠喂食含有0.5%和2% TLE或无TLE对照（AIN-76）的饮食。使用葡聚糖硫酸钠（DSS）暴露小鼠和IL-10−/−;NF-κBEGFP小鼠（分别代表急性和自发性慢性结肠炎模型）评估TLE饮食的疗效。使用微型内窥镜确定宏观粘膜病变的程度。使用小鼠脾细胞和肠上皮细胞来确定TLE对LPS诱导的NF-κB信号传导的体外影响。TLE可抑制LPS诱导的IEC-18细胞IκBα降解、RelA转位、NF-κB转录活性和MIP-2 mRNA的积累。此外，LPS诱导的IL-12 p40基因表达在TLE处理的脾细胞中呈剂量依赖性抑制。有趣的是，通过体重减轻、结肠镜分析和组织学评分测量，与对照饮食相比，饲喂TLE的NF-κBEGFP小鼠中DSS诱导的急性结肠炎恶化。相反，与对照饮食相比，TLE喂养的IL-10−/−;NF-κBEGFP小鼠显示结肠EGFP表达降低。与对照饮食相比，IL-6、TNFα和MCP-1 mRNA表达在饲喂TLE、暴露于DSS的NF-κBEGFP小鼠的结肠中增加。此外，与DSS对照小鼠相比，在TLE饮食喂养的DSS暴露小鼠中，caspase-3活化和TUNEL阳性细胞增强。这些结果表明，TLE通过阻断NF-κB信号传导来阻止LPS诱导的促炎基因表达，但通过增强上皮细胞凋亡来减轻DSS诱导的结肠炎。
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. 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-κBEGFP 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-κB signaling. In vitro, TLE blocked LPS-induced IκBα degradation, RelA translocation, NF-κB 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-κBEGFP mice compared to control diet as measured by weight loss, colonoscopic analysis and histological scores. In contrast, TLE-fed IL-10−/−;NF-κBEGFP mice displayed decreased colonic EGFP expression compared to control diet. IL-6, TNFα, and MCP-1 mRNA expression were increased in the colon of TLE-fed, DSS-exposed NF-κBEGFP 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. These results indicate that TLE prevents LPS-induced proinflammatory gene expression by blocking of NF-κB signaling, but aggravates DSS-induced colitis by enhancing epithelial cell apoptosis.