The role of microglia in the pathogenesis of the central nervous system

本研究旨在探讨小胶质细胞的起源和功能，小胶质细胞在中枢神经系统（CNS）细胞因子网络中的作用以及在CNS疾病的病理生理学中的作用。正如外周巨噬细胞一样，小胶质细胞的增殖和分化受到集落刺激因子的调控。然而，巨噬细胞失活细胞因子如IL-4、IL-10和TGF β对小胶质细胞的作用不同于对巨噬细胞的作用。所有三种细胞因子抑制CNS细胞的细胞因子产生。但IL-4诱导小胶质细胞增殖，而不诱导巨噬细胞增殖。IL-10下调小胶质细胞中细胞因子受体的表达，但不下调巨噬细胞中细胞因子受体的表达。由于我们已经表明IL-10是由小胶质细胞和星形胶质细胞产生的，并且受体由这些细胞表达，因此这些细胞因子可能在CNS细胞因子网络中作为负调节剂发挥作用，其功能与外周免疫系统不同。我们还发现胶质细胞产生IL-5，其功能尚不清楚。虽然CNS中产生多种细胞因子，但大多数是在病理条件下诱导产生的。我们仅在正常成人脑组织中检测到IL-1、TNF α和M-CSF mRNA。我们还发现小胶质细胞产生细胞因子的反应比其他胶质细胞快得多，并且小胶质细胞产生的细胞因子如TNF α或IL-1诱导星形胶质细胞产生IL-6。总之，我们假设小胶质细胞具有一些不同于巨噬细胞的特征，并且在CNS中的细胞因子网络中发挥主要的调节作用。

In this study we aimed to approach the origin and function of microglia, roles of microglia in the cytokine network in the central nervous system (CNS) and in the pathophysiology of CNS disorders. Microglia was shown to be regulated for their proliferation and differentiation by colony stimulating factor as was peripheral macrophages. However, the effects of macrophage-deactivating cytokines such as IL-4, IL-10 and TGFbeta on microglia were different from those on macrophages. All three cytokines suppressed cytokine production by CNS cells. But, IL-4 induced proliferation of microglia but not in macrophages. IL-10 down-regulated the expression cytokine receptors in microglia but not in macrophages. Since we have shown that IL-10 is produced by microglia and astrocytes and the receptors are expressed by these cells, these cytokines may play a role in the CNS cytokine network as a negative regulators, functioning differently from peripheral immune system. We also found that the glial cells produced IL-5 whose functions are as yet unknown.Although a variety of cytokines are produced in the CNS,most of them were induced in the pathological conditions. We only detect IL-1, TNFalpha and M-CSF mRNA in the normal adult brain. We also found the microglia responded to produce cytokine much faster than other glial cells and the cytokine produced by microglia such as TNFalpha or IL-1 induced IL-6 production in astrocytes. Taking altogether, we assume microglia have some different characteristic from macrophages and play a major regulatory role in the cytokine network in the CNS.