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Tumor necrosis factor alpha is not implicated in the genesis of experimental autoimmune gastritis.
Journal of Autoimmunity ( IF 12.8 ) Pub Date : 2004-01-08 , DOI: 10.1016/j.jaut.2003.09.003
Aiden C J Marshall 1 , Ban-Hock Toh , Frank Alderuccio
Affiliation  

Experimental autoimmune gastritis (EAG) characterised by mononuclear cell infiltrate, parietal and zymogenic cell destruction and circulating autoantibodies to gastric H(+)/K(+)ATPase is an animal model for human autoimmune gastritis, that leads to pernicious anaemia. We have previously shown that Fas has a role in initiating damage to target cells in EAG. Here we used three strategies to examine the role of TNFalpha in this disease. We administered neutralising anti-TNFalpha antibody either as a single injection or as twice weekly injections for 8 weeks to mice subjected to neonatal thymectomy-induced EAG. To address the role of apoptotic signals through TNFR1, TNFR1 deficient mice were either neonatally thymectomised or crossed to PC-GMCSF transgenic mice that spontaneously develop EAG. Neonatally thymectomised mice treated with anti-TNFalpha antibody developed destructive gastritis and autoantibodies to gastric H(+)/K(+)ATPase similar to control mice. Following either neonatal thymectomy or crossing to PC-GMCSF transgenic mice, TNFR1 deficient mice developed autoantibody-positive destructive gastritis at similar frequency compared with wild type and heterozygous littermates. Our observations that neutralisation of TNFalpha and absence of TNFR1 has no discernible effect on development of EAG suggest that TNFalpha is not required for mucosal cell damage or development of autoimmune gastritis. While blocking TNFalpha activity has therapeutic benefit in certain autoimmune diseases, this is not the case for EAG.

中文翻译:

肿瘤坏死因子α不参与实验性自身免疫性胃炎的发生。

实验性自身免疫性胃炎(EAG)的特征是单核细胞浸润,壁细胞和产酶细胞的破坏以及针对胃H(+)/ K(+)ATPase的循环自身抗体是人类自身免疫性胃炎的动物模型,可导致恶性贫血。先前我们已经证明Fas在引发EAG中靶细胞损伤方面具有作用。在这里,我们使用三种策略来检查TNFalpha在这种疾病中的作用。我们以单次注射或每周两次两次的方式将中和性抗TNFα抗体给药至经历了新生胸腺切除术诱导的EAG的小鼠,共8周。为了解决凋亡信号通过TNFR1的作用,将TNFR1缺陷的小鼠进行新生儿胸腺切除术或与自发形成EAG的PC-GMCSF转基因小鼠杂交。用抗TNFα抗体处理的新生儿经胸腺切除的小鼠与对照小鼠相似,形成破坏性胃炎和针对胃H(+)/ K(+)ATPase的自身抗体。在新生儿胸腺切除术或与PC-GMCSF转基因小鼠杂交后,与野生型和杂合同窝仔相比,缺乏TNFR1的小鼠发展出自身抗体阳性的破坏性胃炎的频率相似。我们的观察发现,TNFα的中和作用和不存在TNFR1对EAG的发展没有明显的影响,这表明TNFalpha不需要用于粘膜细胞损伤或自身免疫性胃炎的发展。虽然阻断TNFalpha活性在某些自身免疫性疾病中具有治疗益处,但EAG并非如此。在新生儿胸腺切除术或与PC-GMCSF转基因小鼠杂交后,与野生型和杂合同窝仔相比,缺乏TNFR1的小鼠发展出自身抗体阳性的破坏性胃炎的频率相似。我们的观察发现,TNFα的中和作用和不存在TNFR1对EAG的发展没有明显的影响,这表明TNFalpha不需要用于粘膜细胞损伤或自身免疫性胃炎的发展。虽然阻断TNFalpha活性在某些自身免疫性疾病中具有治疗益处,但EAG并非如此。在新生儿胸腺切除术或与PC-GMCSF转基因小鼠杂交后,与野生型和杂合同窝仔相比,缺乏TNFR1的小鼠发展出自身抗体阳性的破坏性胃炎的频率相似。我们的观察结果表明,TNFα的中和作用和对EAG的发育没有明显的影响,这表明TNFalpha不需要用于粘膜细胞损伤或自身免疫性胃炎的发展。虽然阻断TNFalpha活性在某些自身免疫性疾病中具有治疗益处,但EAG并非如此。我们的观察结果表明,TNFα的中和作用和对EAG的发育没有明显的影响,这表明TNFalpha不需要用于粘膜细胞损伤或自身免疫性胃炎的发展。虽然阻断TNFalpha活性在某些自身免疫性疾病中具有治疗益处,但EAG并非如此。我们的观察结果表明,TNFα的中和作用和对EAG的发育没有明显的影响,这表明TNFalpha不需要用于粘膜细胞损伤或自身免疫性胃炎的发展。虽然阻断TNFalpha活性在某些自身免疫性疾病中具有治疗益处,但EAG并非如此。
更新日期:2019-11-01
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