Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais Minas Gerais, Belo Horizonte, MG, Brazil.
Clin Exp Allergy. 2010 Oct;40(10):1541-51. doi: 10.1111/j.1365-2222.2010.03502.x.
Around 300 million people world-wide suffer from asthma, and the prevalence of allergic diseases has increased. Much effort has been used in the study of mechanisms involved in the immune response observed in asthma to intervene for the treatment of this condition. During inflammation in asthma, Th2 cytokines and eosinophils are essential components of the host immune system. Furthermore, for therapeutic interventions against this disease, IL-10 is an important cytokine because it has a central role in the regulation of inflammatory cascades.
To evaluate the immunomodulatory effect of Lactococcus lactis strains expressing recombinant IL-10 in a mouse model of ovalbumin (OVA)-induced acute airway inflammation.
L. lactis expressing recombinant IL-10 in a cytoplasmic (LL-CYT) or secreted form (LL-SEC) and wild-type (LL-WT) were used. IL-10 production by the recombinant strains was evaluated by ELISA. After an intranasal administration of L. lactis producing recombinant IL-10 and the induction of acute allergic airway inflammation in mice, blood samples were collected to detect IgE anti-OVA, and bronchoalveolar lavage (BAL) was harvested for eosinophil count. Additionally, the lungs were collected for the detection of the eosinophil peroxidase (EPO) activity, measurement of cytokines and chemokines and evaluation of pathology.
Mice that received LL-CYT and LL-SEC strains showed a significant decrease in eosinophils numbers, EPO activity, anti-OVA IgE and IgG1 levels, IL-4 and CCL3 production and pulmonary inflammation and mucus hypersecretion, compared with the asthmatic group. Only the LL-CYT/OVA group showed reduced levels of IL-5, CCL2, CCL5 and CCL11.
Treatment with L. lactis producing recombinant IL-10 used in this study (LL-CYT and LL-SEC) modulated experimental airway inflammation in the mouse model independently of Treg cells. Additionally, the LL-CYT strain was more efficient in the suppression of lung inflammation.
全球约有 3 亿人患有哮喘，过敏疾病的患病率也在不断增加。人们在研究哮喘中观察到的免疫反应机制方面付出了巨大努力，以期能够对此类疾病进行干预治疗。在哮喘炎症期间，Th2 细胞因子和嗜酸性粒细胞是宿主免疫系统的重要组成部分。此外，对于针对这种疾病的治疗干预，IL-10 是一种重要的细胞因子，因为它在调节炎症级联反应中起着核心作用。
评估表达重组白细胞介素 10（IL-10）的乳球菌（Lactococcus lactis）菌株在卵清蛋白（OVA）诱导的急性气道炎症小鼠模型中的免疫调节作用。
使用表达重组 IL-10 的细胞质（LL-CYT）或分泌型（LL-SEC）乳球菌以及野生型（LL-WT）乳球菌。通过 ELISA 评估重组菌株的 IL-10 产生情况。在经鼻给予表达重组 IL-10 的乳球菌并诱导小鼠发生急性过敏性气道炎症后，采集血液样本以检测抗 OVA IgE，采集支气管肺泡灌洗液（BAL）以检测嗜酸性粒细胞计数。此外，收集肺组织以检测嗜酸性粒细胞过氧化物酶（EPO）活性、测量细胞因子和趋化因子并评估病理学。
与哮喘组相比，接受 LL-CYT 和 LL-SEC 菌株治疗的小鼠嗜酸性粒细胞数量、EPO 活性、抗 OVA IgE 和 IgG1 水平、IL-4 和 CCL3 产生以及肺部炎症和黏液高分泌均显著降低。只有 LL-CYT/OVA 组的 IL-5、CCL2、CCL5 和 CCL11 水平降低。
本研究中使用的表达重组 IL-10 的乳球菌（LL-CYT 和 LL-SEC）治疗可独立于 Treg 细胞调节小鼠模型中的实验性气道炎症。此外，LL-CYT 菌株在抑制肺部炎症方面更有效。
