Chavany C, Vicario-Abejón C, Miller G, Jendoubi M
Genetics and Molecular Immunology Section, Laboratory of Immunology/National Eye Institute, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda MD 20892, USA.
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11354-9. doi: 10.1073/pnas.95.19.11354.
Interleukin 3 (IL-3) stimulates the proliferation and differentiation of various haematopoietic progenitor cells. Recently, IL-3 and other cytokines were reported to exert a neurotrophic activity and to be associated with neurological disorders, suggesting their complex role in the central nervous system. We now show that overexpression of IL-3 in transgenic mice causes a motor neuron disease with several features of amyotrophic lateral sclerosis and progressive muscular atrophy. These animals exhibit hind limb paralysis at 7 months of age, associated with dendritic and axonal degeneration, loss of motor neurons in the spinal cord, and autoimmune reaction against these cells. We examined the effect of IL-3 on embryonic motor neurons survival in mixed spinal cord cultures. Our results suggest that motor neuronal degeneration is not directly triggered by the high level of expression of IL-3.
白细胞介素3(IL-3)可刺激各种造血祖细胞的增殖和分化。最近,有报道称IL-3和其他细胞因子具有神经营养活性,并与神经疾病有关,这表明它们在中枢神经系统中发挥着复杂的作用。我们现在发现,转基因小鼠中IL-3的过表达会导致一种运动神经元疾病,具有肌萎缩侧索硬化症和进行性肌肉萎缩的若干特征。这些动物在7个月大时出现后肢麻痹,伴有树突和轴突退化、脊髓运动神经元丧失以及针对这些细胞的自身免疫反应。我们研究了IL-3对混合脊髓培养物中胚胎运动神经元存活的影响。我们的结果表明,运动神经元的退化并非由IL-3的高水平表达直接引发。