Chair and Department of Experimental and Clinical Physiology, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
Arch Immunol Ther Exp (Warsz). 2023 Mar 24;71(1):10. doi: 10.1007/s00005-023-00675-y.
Microglia are the resident immune cells of the central nervous system, playing a role in the inflammatory process development and resolution, presenting two main phenotypes, pro-inflammatory M1, and anti-inflammatory M2. Therapies affecting the microglia phenotype may be beneficial in treating inflammatory neurodegenerative diseases. In our experiments, we used the animal multiple sclerosis model, experimental allergic encephalomyelitis (EAE). Rats were treated during the pre- or symptomatic phase of the disease with cyclophosphamide, followed by hematopoietic stem cell transplantation, and with/without post-transplantation cyclophosphamide. Our study aimed to analyze the microglia phenotype in animals subjected to this treatment. The number of M1 cells in the spinal cord, and inducible nitric oxide synthase (iNOS) levels in the brain were similar in all experimental groups. The differences were observed in M2 cells number and arginase 1 (Arg1) levels, which were decreased in EAE animals, and increased after treatment in the symptomatic phase of EAE, and in the pre-symptomatic phase, but only with post-transplantation cyclophosphamide. Analysis of gene expression in the brain showed decreased iNOS expression in EAE animals treated in the symptomatic phase of EAE and no differences in Arg1 expression. Results indicate that treatment applied to experimental animals influences the microglia phenotype, promoting differentiation towards M2 cells.
小胶质细胞是中枢神经系统的固有免疫细胞，在炎症过程的发展和解决中发挥作用，呈现出两种主要表型，促炎型 M1 和抗炎型 M2。影响小胶质细胞表型的治疗方法可能有益于治疗炎症性神经退行性疾病。在我们的实验中，我们使用了动物多发性硬化模型，实验性自身免疫性脑脊髓炎（EAE）。在疾病的前症状或症状期，大鼠用环磷酰胺治疗，然后进行造血干细胞移植，并在移植后进行/不进行环磷酰胺治疗。我们的研究旨在分析接受这种治疗的动物中小胶质细胞的表型。脊髓中的 M1 细胞数量和大脑中的诱导型一氧化氮合酶（iNOS）水平在所有实验组中相似。在 M2 细胞数量和精氨酸酶 1（Arg1）水平上观察到差异，EAE 动物的 Arg1 水平降低，EAE 症状期治疗后增加，在 EAE 前症状期增加，但仅在移植后进行环磷酰胺治疗后增加。对大脑中基因表达的分析表明，在 EAE 症状期治疗的实验动物中 iNOS 表达降低，Arg1 表达无差异。结果表明，应用于实验动物的治疗方法影响小胶质细胞表型，促进向 M2 细胞分化。
