Western-style diets induce macrophage infiltration and contribute to colitis-associated carcinogenesis
Western-style diets induce macrophage infiltration and contribute to colitis-associated carcinogenesis
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DOI：
10.1111/j.1440-1746.2010.06332.x
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发表时间：
2010-11-01
影响因子：
4.1
通讯作者：
Kim, Jin-Ho
中科院分区：
文献类型：
--
作者：
Kim, In-Wha;Myung, Seung-Jae;Kim, Jin-Ho
背景与目的：西式饮食在炎症性肠病和结肠癌发生中起重要作用。本研究的目的是了解巨噬细胞在与致癌性相关的wd诱导结肠炎中的作用。方法：雄性BALB/c小鼠分别饲喂WD或对照日粮（CD） 4周，偶氮氧甲烷（AOM）和2%葡聚糖硫酸钠（DSS）连续7 d。结果：WD增加了dss诱导炎症的易感性，加速了巨噬细胞的浸润。WD组小鼠结肠肿瘤的发生率和多样性明显高于CD组（P < 0.05）。经AOM和DSS处理后，WD小鼠结肠中前列腺素内过氧化物合成酶（PTGS） 2和前列腺素E-2水平均高于CD小鼠。WD消耗增加了核因子- kappab的DNA结合活性和血清中肿瘤坏死因子(TNF)- α的浓度。饲喂WD的小鼠癌细胞周围f4 /80阳性细胞数量高于饲喂CD的小鼠，这些细胞表达PTGS2、tnf - α和β -catenin，这些细胞被WD上调。我们还发现，WD增加了结肠癌细胞细胞质和细胞核中未磷酸化的β -连环蛋白的积累。结论：WD增加dss诱导炎症的易感性，加速巨噬细胞的浸润。反过来，这导致了结肠癌的发生和发展。
Background and Aim:A Western-style diet (WD) is known to play an important role in inflammatory bowel disease and colon carcinogenesis. The purpose of this study was to understand the role of macrophages in WD-induced colitis associated with carcinogenesis.Methods:Male BALB/c mice were fed a WD or a control diet (CD) for 4 weeks and exposed to azoxymethane (AOM) followed by 2% dextran sulfate sodium (DSS) for 7 days.Results:The WD increased susceptibility to DSS-induced inflammation and accelerated the infiltration of macrophages. The incidence and multiplicity of colon tumors were higher in mice fed the WD than in those fed the CD (P < 0.05). Levels of prostaglandin-endoperoxide synthase (PTGS) 2 and prostaglandin (PG) E-2 in the colon were higher after treatment with AOM and DSS in mice fed the WD than in those fed the CD. In addition, WD consumption increased the DNA binding activity of nuclear factor-kappaB and the serum concentration of tumor necrosis factor (TNF)-alpha. Mice fed the WD had higher numbers of F4/80-positive cells surrounding cancer cells compared with mice fed the CD. These cells expressed PTGS2, TNF-alpha and beta-catenin, which are up-regulated by the WD. We also found that the WD increased unphosphorylated beta-catenin accumulation in the cytoplasm and nucleus of colon cancer cells.Conclusions:A WD increases the susceptibility to DSS-induced inflammation and accelerates the infiltration of macrophages. In turn, this resulted in the development and progression of colon cancer.