The Role of the Tumor Necrosis Factor Receptor in 2,4,6-Trinitrobenzene Sulphonic Acid (TNBS)-induced Colitis in Mice

肿瘤坏死因子受体在 2,4,6-三硝基苯磺酸 (TNBS) 诱导的小鼠结肠炎中的作用

• 批准号: 15590635
• 负责人: KATO Tomohiro
• 金额: $ 2.24万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590635/
• 关键词: Inflammatory Bowel Disease; TNFR-KO mouse; Proteome; TNF-α; NF-kB; 炎症性腸モデル; Trinitrobenzene suiphonic acid (TNBS); TNF; NF-κB; 実験的大腸炎モデル; TNFRノックアウトマウス

It is well known that tumor necrosis factor (TNF) plays a key role in the immunopathogenesis of inflammatory bowel disease (IBD) ; the mechanism, however, has not yet been defined. To elucidate the role of the TNF receptor in IBD, we investigated the effect of administering an enema containing 2,4,6-trinitrobenzene sulphonic acid (TNBS), which produces many histological and immunological conditions similar to those of Crohn's disease, using wild (WT), TNFR-1KO, TNFR-2KO and TNFR-1,2KO C57BL/6 strain mice. Mice were irrigated with 6 mg of TNBS into the colon via the anus and sacrificed one week later. In the histological assessment, inflammatory cell scores showed no significant differences among all TNBS-administered groups, whereas tissue damage scores were significantly lower in TNFR-1KO and TNFR-1,2KO mice than in WT mice. The apoptotic indexes of mononuclear cells in the lamina propria of all TNBS-administered groups assessed by TUNEL straining were significantly lower than that of controls. Serum TNF levels of all TNBS-administered groups did not differ significantly from that of, controls, whereas TNF-a mRNA expression in the colon was significantly higher in all TNBS-administered groups than in controls. Further, NF-kb activities were enhanced in WT and TNFR-2KO mice compared with those in control mice. In conclusion, the present data suggest that continuous infiltration of inflammatory cells is substantially responsible for the pathogenesis of TNBS-colitis in mice, which is closely associated with defective apoptosis of mononuclear cells in the lamina propria but not with the TNF/TNFR signaling system.

众所周知，肿瘤坏死因子（TNF）在炎症性肠病（IBD）的免疫发病机制中起着关键作用；然而，这一机制尚未明确。为了阐明TNF受体在IBD中的作用，我们研究了使用野生（WT）、TNFR-1KO、TNFR-2KO和tnfr - 1,2ko C57BL/6菌株小鼠给予含有2,4,6-三硝基苯磺酸（TNBS）的灌肠剂的效果，TNBS产生许多类似于克罗恩病的组织学和免疫学状况。将6mg TNBS经肛门灌入小鼠结肠，一周后处死。在组织学评估中，炎症细胞评分在所有tnbs给药组之间没有显着差异，而TNFR-1KO和tnfr - 1,2ko小鼠的组织损伤评分明显低于WT小鼠。TUNEL染色观察各给药组大鼠固有层单核细胞凋亡指标均显著低于对照组。所有tnbs给药组的血清TNF水平与对照组没有显著差异，而结肠中TNF-a mRNA的表达在所有tnbs给药组中均显著高于对照组。此外，与对照组小鼠相比，WT和TNFR-2KO小鼠的NF-kb活性增强。综上所述，目前的数据表明，炎症细胞的持续浸润是小鼠tnbs -结肠炎发病的重要原因，它与固有层单个核细胞凋亡缺陷密切相关，而与TNF/TNFR信号系统无关。

项目成果

The Role of the Tumor Necrosis Factor Receptor in 2,4,6-Trinitrobenzene Sulphonic Acid (TNBS)-Induced Colitis in Mice.

肿瘤坏死因子受体在 2,4,6-三硝基苯磺酸 (TNBS) 诱导的小鼠结肠炎中的作用。

• 发表时间: 2005
• 期刊: Dig.Dis. Sci. 50
• 作者: Minoru Nakai