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

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，但其机制尚未明确。为了阐明肿瘤坏死因子受体在IBD中的作用，我们用野生型(WT)、TNFR-1KO、TNFR-2KO和TNFR-1，2KO C57BL/6品系小鼠，研究了含有2，4，6-三硝基苯磺酸(TNBS)的灌肠对IBD的影响。小鼠经肛门向结肠内注入6 mg TNBS，一周后处死。在组织学评估中，所有TNBS组的炎性细胞评分没有显著差异，而组织损伤评分在TNFR-1KO和TNFR-1，2KO组显著低于WT组。TUNEL法检测TnBS各剂量组固有层单个核细胞的凋亡指数均显著低于对照组。所有给药组的血清肿瘤坏死因子水平与对照组没有显著差异，而结肠组织中的肿瘤坏死因子-αmRNA表达在所有给药组显著高于对照组。此外，WT组和TNFR-2KO组小鼠的核因子-kb活性均高于对照组。综上所述，目前的数据表明，炎症细胞的持续渗透是小鼠TNBS-结肠炎的重要原因，而与固有层单个核细胞的缺陷凋亡密切相关，而与肿瘤坏死因子/肿瘤坏死因子受体信号系统无关。

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.