Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerai, Av. Antônio Carlos, 6627, Pampulha, 31, Belo Horizonte, MG, 270-901, Brazil.
Laboratório de Imunobiologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerai, Belo Horizonte, Minas Gerais, Brazil.
BMC Biotechnol. 2020 Jul 23;20(1):38. doi: 10.1186/s12896-020-00631-0.
Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract (GIT) and to date, no efficient treatments exist. Interleukin-10 (IL-10), one of the most important anti-inflammatory cytokines of the immune response, has been under study due to its potential for IBD therapy; however, systemic treatments lead to undesirable side effects and oral administration is limited due to its quick degradation. To avoid these bottlenecks, we previously engineered an invasive Lactococcus lactis (L. lactis) strain capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac:il-10) that diminished inflammation in two induced mouse models of intestinal inflammation. Thus, the aim of this study was to analyze its therapeutic effect in the IL-10-deficient mouse model (IL-10) that spontaneously and gradually develops an inflammation that modifies the immune system and resembles Crohn's disease (CD) in humans, and evaluate if it would also diminish and/or prevent the onset of this disease.
Oral administration of L. lactis MG1363 FnBPA+ (pValac:il-10) to IL-10 mice not only led to IL-10 production by these, but consequently also diminished the severe development of the disease, with animals showing lower macroscopic scores and histological damages, increased IL-10 levels and tendency to lower pro-inflammatory cytokine levels.
The results of this study, together with the previously published ones using this DNA delivery-based strategy, show that it is capable of creating and maintaining an anti-inflammatory environment in the GIT and thus effectively diminish the onset of inflammation in various mouse models.
炎症性肠病（IBD）是一种胃肠道（GIT）炎症性疾病，迄今为止尚无有效的治疗方法。白细胞介素-10（IL-10）是免疫反应中最重要的抗炎细胞因子之一，由于其在 IBD 治疗中的潜力而受到研究关注；然而，全身治疗会导致不良副作用，口服给药因其快速降解而受到限制。为了避免这些瓶颈，我们之前构建了一种侵袭性乳球菌（L. lactis）菌株，能够将编码 Mus musculus（pValac:il-10）的真核 DNA 表达载体直接递送到宿主细胞中，该载体编码的 IL-10 可减少两种诱导的肠道炎症小鼠模型中的炎症。因此，本研究的目的是分析其在 IL-10 缺陷型小鼠模型（IL-10）中的治疗效果，该模型自发且逐渐发展为一种炎症，改变免疫系统，类似于人类的克罗恩病（CD），并评估其是否也会减轻和/或预防这种疾病的发生。
口服给予 L. lactis MG1363 FnBPA+（pValac:il-10）可导致这些动物产生 IL-10，从而减轻疾病的严重发展，动物的宏观评分和组织学损伤降低，IL-10 水平升高，促炎细胞因子水平降低趋势。
本研究的结果与之前使用该 DNA 递送策略发表的结果一起表明，它能够在 GIT 中创建和维持抗炎环境，从而有效减轻各种小鼠模型中炎症的发生。
