Berlec Aleš, Perše Martina, Ravnikar Matjaž, Lunder Mojca, Erman Andreja, Cerar Anton, Štrukelj Borut
Department of Biotechnology, Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia.
Institute of Pathology, Medical Experimental Centre, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
Int Immunopharmacol. 2017 Feb;43:219-226. doi: 10.1016/j.intimp.2016.12.027. Epub 2016 Dec 29.
TNFα 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 TNFα-binding affibody with control Lactococcus lactis and with anti-TNFα 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. TNFα-binding L. lactis was less effective than control L. lactis, particularly when TNFα-binding L. lactis was administered in preventive fashion. Similarly, an apparently detrimental effect of TNFα neutralization was observed in mice that were intraperitoneally administered anti-TNFα monoclonal antibody infliximab prior to colitis induction. The highest concentrations of tissue TNFα were observed in groups without DSS colitis that were treated either with TNFα-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 TNFα aggravated disease symptoms in the acute phase of colitis and increased TNFα concentration in colon tissue of healthy mice. Nevertheless, we have demonstrated that oral administration of bacteria with surface displayed TNFα-binding affibody can interfere significantly with TNFα signaling and mimic the infliximab response in the given animal model of colitis.
肿瘤坏死因子α（TNFα）在炎症性肠病中具有明确作用，炎症性肠病会影响胃肠道，通常表现为克罗恩病或溃疡性结肠炎。我们将展示TNFα结合亲和体的乳酸乳球菌NZ9000与对照乳酸乳球菌以及抗TNFα抗体英夫利昔单抗进行了比较，用于治疗葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎。在用DSS诱导结肠炎一周后，乳酸乳球菌NZ9000减轻了结肠炎的严重程度，在DSS给药前、给药期间和给药后预防性给药时效果更显著。结合TNFα的乳酸乳球菌比对照乳酸乳球菌效果差，尤其是在预防性给药时。同样，在结肠炎诱导前腹腔注射抗TNFα单克隆抗体英夫利昔单抗的小鼠中观察到TNFα中和有明显的有害作用。在未患DSS结肠炎但用结合TNFα的乳酸乳球菌或英夫利昔单抗治疗的组中观察到组织TNFα浓度最高。总之，我们证实了乳酸乳球菌对DSS诱导的小鼠结肠炎具有保护作用。与预期相反，但与一些报道一致，TNFα的中和在结肠炎急性期加重了疾病症状，并增加了健康小鼠结肠组织中的TNFα浓度。然而，我们已经证明，口服表面展示TNFα结合亲和体的细菌可以显著干扰TNFα信号传导，并在给定的结肠炎动物模型中模拟英夫利昔单抗的反应。
