Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor α
Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor α
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DOI：
10.1016/j.intimp.2016.12.027
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发表时间：
2017-02-01
影响因子：
5.6
通讯作者：
Strukelj, Borut
中科院分区：
文献类型：
--
作者：
Berlec, Aies;Perse, Martina;Strukelj, Borut
TNF α在影响胃肠道的炎症性肠病中具有明确的作用，通常表现为克罗恩病或溃疡性结肠炎。我们比较了乳酸乳球菌NZ9000展示TNF α结合抗体与对照乳酸乳球菌和抗TNF α抗体英夫利昔单抗治疗葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠。L.在用DSS诱导结肠炎后一周，乳酸菌NZ9000减轻了结肠炎的严重程度，当在DSS施用之前、期间和之后以预防方式施用时更有效。结合TNF α的乳酸菌比对照乳酸菌效果差，特别是当结合TNF α的乳酸菌。以预防性方式施用乳酸。同样，在结肠炎诱导前腹腔内给予抗TNF α单克隆抗体英夫利西单抗的小鼠中观察到TNF α中和的明显有害作用。组织TNF α的最高浓度在没有DSS结肠炎的组中观察到，这些组用TNF α结合L.乳酸或英夫利昔单抗。最后，我们证实了L。lactis对DSS诱导的小鼠结肠炎具有保护作用。与预期相反，但与一些报告一致，TNF α的中和加重了结肠炎急性期的疾病症状，并增加了健康小鼠结肠组织中的TNF α浓度。尽管如此，我们已经证明，口服具有表面展示TNF α结合抗体的细菌可以显著干扰TNF α信号传导，并在给定的结肠炎动物模型中模拟英夫利西单抗反应。(C)2016爱思唯尔B.V.保留所有权利。
TNF alpha has a well-established role in inflammatory bowel disease that affects the gastrointestinal tract and is usually manifested as Crohn's disease or ulcerative colitis. We have compared Lactococcus lactis NZ9000 displaying TNF alpha-binding affibody with control Lactococcus lactis and with anti-TNF alpha antibody infliximab for the treatment of mice with dextran sulphate sodium (DSS)-induced colitis. L. lactis NZ9000 alleviated the colitis severity one week after colitis induction with DSS, more effectively when administered in preventive fashion prior to, during and after DSS administration. TNF alpha-binding L lactis was less effective than control L lactis, particularly when TNF alpha-binding L. lactis was administered in preventive fashion. Similarly, an apparently detrimental effect of TNF alpha neutralization was observed in mice that were intraperitoneally administered anti-TNF alpha monoclonal antibody infliximab prior to colitis induction. The highest concentrations of tissue TNF alpha were observed in groups without DSS colitis that were treated either with TNF alpha-binding L. lactis or infliximab. To conclude, we have confirmed that L. lactis exerts a protective effect on DSS-induced colitis in mice. Contrary to expectations, but in line with some reports, the neutralization of TNF alpha aggravated disease symptoms in the acute phase of colitis and increased TNF alpha concentration in colon tissue of healthy mice. Nevertheless, we have demonstrated that oral administration of bacteria with surface displayed TNF alpha-binding affibody can interfere significantly with TNF alpha signaling and mimic the infliximab response in the given animal model of colitis. (C) 2016 Elsevier B.V. All rights reserved.