Predominant T helper type 2-inflammatory responses promote murine colon cancers
Predominant T helper type 2-inflammatory responses promote murine colon cancers
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DOI：
10.1002/ijc.21639
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发表时间：
2006-05-01
影响因子：
6.4
通讯作者：
Dohi, T
中科院分区：
文献类型：
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作者：
Osawa, E;Nakajima, A;Dohi, T
结肠癌是炎症性肠病，尤其是溃疡性结肠炎（UC）最严重的并发症之一。以往的研究表明，UC炎症过程中的特征性免疫事件是T辅助细胞2型（Th 2）细胞衍生的细胞因子的表达。在这项研究中，我们研究了结肠炎中占主导地位的Th 2型细胞因子反应对致癌物诱导的结肠肿瘤的影响。本研究使用BALB/c背景的野生型（WT）、干扰素γ（IFN-γ）基因缺陷型（-/-）[Th 2显性]或白细胞介素（IL）-4（-/-）[Th 1显性]小鼠。为了比较肿瘤形成，小鼠被给予致癌物氧化偶氮甲烷（AOM）和直肠内给予三硝基苯磺酸（TNBS），以诱导结肠炎。初始治疗后33周，检查全结肠。当用AOM和TNBS处理IFN-γ（-/-）小鼠时，观察到的肿瘤数量（8.4 +/-1.7）显著高于接受相同处理的WT（3.3 +/-2.9）或IL-4（-/-）（3.1 +/-3.4）小鼠。使用较少剂量的AOM和TNBS的一组单独的实验也显示IFN-γ（-/-）小鼠中肿瘤形成的频率高于IL-4（-/-）小鼠。组织学上，肿瘤是高分化或中等分化腺癌。未见肠粘膜下层或浆膜层浸润。在免疫组织学染色中，IFN-γ（-/-）小鼠中的一些肿瘤显示出β-连环蛋白的明显核表达，与IL-4-/-小鼠肿瘤中观察到的强膜染色相反。总之，与Th 2-donimant细胞因子反应相关的结肠炎症促进了恶性肿瘤的形成。(c)2005 Wiley-Liss，Inc.
Colon cancer is one of the most serious complications of inflammatory bowel diseases, especially ulcerative colitis (UC). Previous studies have shown that characteristic immunological event during inflammation in UC is the expression of T helper-type 2 (Th2) cell-derived cytokines. In this study, we investigated the influence of a predominant Th2-type cytokine response in colitis on carcinogen-induced colon tumors. Wild type (WT), interferon gamma (IFN-gamma) gene deficient (-/-) [Th2 dominant] or interleukin (IL)-4(-/-) [Th1-dominant] mice of BALB/c background were used in this study. To compare tumor formation, mice were given the carcinogen azoxymethane (AOM) and intrarectal administration of trinitrobenzene sulfonic acid (TNBS), to induce colitis. Thirty-three weeks after initial treatment, the total colon was examined. When IFN-gamma(-/-) mice were treated with AOM and TNBS, significantly higher number of tumors were seen (8.4 +/- 1.7) than in WT (3.3 +/- 2.9) or IL-4(-/-) (3.1 +/- 3.4) mice, which received identical treatments. A separate set of experiment, using less doses of AOM and TNBS also showed the higher frequency of tumor formation in IFN-gamma(-/-) mice than in IL-4(-/-) mice. Histulogically, the tumors were well- or moderately-differentiated adenocarcinomas. No invasion into the submucosal or serosal layers of the intestine was seen. In immunohistological staining, some tumors in IFN-gamma(-/-) mice showed distinct nuclear expression of beta-catenin, in contrast to the strong membrane staining seen in tumors of IL-4-/- mice. In conclusion, colonic inflammation associated with Th2-donimant Cytokine responses enhanced the formation of malignant neoplasms. (c) 2005 Wiley-Liss, Inc.