Role of TNF Receptors, TNFR1 and TNFR2, in Dextran Sodium Sulfate-Induced Colitis
Role of TNF Receptors, TNFR1 and TNFR2, in Dextran Sodium Sulfate-Induced Colitis
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DOI：
10.1002/ibd.20951
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发表时间：
2009-10-01
影响因子：
4.9
通讯作者：
Stadnyk, Andrew W.
中科院分区：
文献类型：
--
作者：
Stillie, RoseMarie;Stadnyk, Andrew W.
背景：在本研究中，我们确定了在葡聚糖硫酸钠(DSS)结肠炎模型中每个肿瘤坏死因子受体TNFR1或TNFR2缺失的后果。方法：野生型(WT)、TNFR1(-/-)和TNFR2(-/-)小鼠在饮水中喂养5天，然后饮用自来水2(7天)或7(12天)。结果：未处理的TNFRI-/-和TNFR2(-/-)小鼠的结肠组织学正常。在DSS之后，所有菌株都发炎了。与WT和TNFR2(-/-)小鼠相比，TNFR1(-/-)小鼠在第8天和第9天的临床评分更严重，尽管它们的结肠组织病理损害相似。临床评分越重，巨噬细胞对结肠粘膜的浸润越少。在第7天，与TNFR1(-/-)和WT品系相比，TNFR2(-/-)小鼠表现出更多的疾病指标，包括结肠重量增加，盲肠缩小，溃疡数量增加。与非炎症对照组相比，结肠炎小鼠的粘膜TNFR2水平升高，在第7天，品系之间没有差异，但在第12天，与WT小鼠不同，TNFR1(-/-)小鼠的粘膜水平降低。用结肠匀浆Western印迹法检测，不同菌株间TUNEL阳性的凋亡结肠上皮细胞数目和caspase3的总裂解水平均无差异。结论：虽然两种受体的缺失都与DSS结肠炎的某些指标有关，但组织病理学评分相似，表明肿瘤坏死因子受体在DSS结肠炎的病理过程中要么不起主要作用，要么是多余的。
Background: In this study we determined the consequence of the absence of each TNF receptor, TNFR1 or TNFR2, in the dextran sulfate sodium (DSS) model of colitis.Methods: Wildtype (WT), TNFR1(-/-) and TNFR2(-/-) mice were fed 3% w/v DSS in drinking water for 5 days followed by 2 (day 7) or 7 (day 12) days of tap water.Results: The colons from untreated TNFRI-/- and TNFR2(-/-) mice were histologically normal. Following DSS, all strains became inflamed. TNFR1(-/-) mice had a more severe clinical score at days 8 and 9 compared to WT and TNFR2(-/-) mice despite similar histopathological damage in their colons. The more severe clinical score was associated with a reduced macrophage infiltration into the colonic mucosa. TNFR2(-/-) mice showed increased indicators of disease including increased colon weight, a shrunken cecum, and an increased number of ulcers compared to TNFR1(-/-) and WT strains at day 7. Mucosal levels of TNFR2 were elevated in colitic mice compared to uninflamed controls, with no difference between strains on day 7 but on day 12, unlike WT mice, levels were reduced in TNFR1(-/-) mice. There was no difference in the number of TUNEL-positive apoptotic colonic epithelial cells between strains, nor in total cleaved caspase 3 levels between strains, measured by Western blot of colon homogenates.Conclusions: While deficiency of either receptor contributes to some measures of DSS colitis, the histopathological scores are similar, indicating that TNF receptors either do not play a major role or are redundant in the pathology associated with DSS colitis.