Suppression of intestinal inflammation and inflammation-driven colon cancer in mice by dietary sphingomyelin: importance of peroxisome proliferator-activated receptor γ expression.
Suppression of intestinal inflammation and inflammation-driven colon cancer in mice by dietary sphingomyelin: importance of peroxisome proliferator-activated receptor γ expression.
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DOI：
10.1016/j.jnutbio.2010.09.017
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发表时间：
2011-12
影响因子：
5.6
通讯作者：
Schmelz, Eva M.
中科院分区：
文献类型：
--
作者：
Mazzei, Joseph C.;Zhou, Hui;Brayfield, Bradley P.;Hontecillas, Raquel;Bassaganya-Riera, Josep;Schmelz, Eva M.
胃肠道炎症会增加患结肠癌的风险，尤其是在年轻人中。膳食化合物不仅与炎症和结肠癌的病因学有关，而且还与其预防有关。鞘脂代谢物已被证明在炎症反应的启动和持续中发挥作用。在本研究中，我们研究了饮食鞘磷脂对缺乏功能性PPAR-γ n肠上皮和免疫细胞的小鼠中葡聚糖硫酸钠诱导的结肠炎和氧化偶氮甲烷诱导的结肠癌的抑制作用。在两种基因型的小鼠中，饮食鞘磷脂降低了疾病活动和结肠炎性病变，但在表达PPAR-γ的小鼠中更有效。鞘磷脂喂养小鼠的存活率增加和肿瘤形成抑制似乎与免疫和上皮细胞中的PPAR-γ表达无关。使用实时PCR阵列，我们检测到参与Th 1（IFN-γ）和Th 17（IL-17和IL-23）反应的基因上调，尽管炎症评分降低。Th 2（IL-4、IL-13和IL-13 ra 2）和Treg（IL-10 rb）抗炎反应相关基因表达上调，且呈PPAR-γ依赖性。与我们体内发现的PPAR-γ依赖性一致，用鞘氨醇处理RAW巨噬细胞增加了PPAR-γ报告基因活性。总之，膳食鞘磷脂通过激活PPAR-γ调节疾病早期的炎症反应，但其抗癌作用遵循不依赖于PPAR-γ的模式。
Inflammation of the gastrointestinal tract increases the risk of developing colon cancer especially in younger adults. Dietary compounds are not only associated with the etiology of inflammation and colon cancer, but also in their prevention. Sphingolipid metabolites have been shown to play a role in the initiation and perpetuation of inflammatory responses. In the present study, we investigated the suppression of dextran sodium sulfate-induced colitis and azoxymethane-induced colon cancer by dietary sphingomyelin in mice that lack functional PPAR-γ n intestinal epithelial and immune cells. Dietary sphingomyelin decreased disease activity and colonic inflammatory lesions in mice of both genotypes but more efficiently in mice expressing PPAR-γ. The increased survival and suppression of tumor formation in the sphingomyelin-fed mice appeared to be independent of PPAR-γ expression in immune and epithelial cells. Using a real-time PCR array, we detected an up-regulation in genes involved in Th1 (IFN-γ) and Th17 (IL-17 and IL-23) responses despite the reduced inflammation scores. However, the genes involved in Th2 (IL-4, IL-13 and IL-13ra2) and Treg (IL-10rb) anti-inflammatory responses were up-regulated in a PPAR-γ dependent manner. In line with the PPAR-γ dependency of our in vivo findings, treatment of RAW macrophages with sphingosine increased the PPAR-γ reporter activity. In conclusion, dietary sphingomyelin modulated inflammatory responses at early stages of disease by activating PPAR-γ, but its anti-carcinogenic effects followed a PPAR-γ-independent pattern.
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影响因子：
4.2
作者：
Evans, Nicholas P.;Misyak, Sarah A.;Bassaganya-Riera, Josep
通讯作者：
Bassaganya-Riera, Josep
影响因子：
4.3
作者：
Bassaganya-Riera, Josep;Misyak, Sarah;Hontecillas, Raquel
通讯作者：
Hontecillas, Raquel
影响因子：
16
作者：
Barak, Y;Nelson, MC;Evans, RM
通讯作者：
Evans, RM
影响因子：
4.8
作者：
Cui, Y;Miyoshi, K;Hennighausen, L
通讯作者：
Hennighausen, L
影响因子：
6.5
作者：
Bartke, Nana;Hannun, Yusuf A.
通讯作者：
Hannun, Yusuf A.