Aloisi F, Borsellino G, Caré A, Testa U, Gallo P, Russo G, Peschle C, Levi G
Department of Organ and System Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
Int J Dev Neurosci. 1995 Jun-Jul;13(3-4):265-74. doi: 10.1016/0736-5748(94)00071-a.
Participation of astrocytes in central nervous system pathophysiology is likely to involve cytokines, both as stimulators and mediators of astrocyte function. We have used highly enriched human astrocyte cultures as an experimental tool to investigate the influence of cytokines on adhesion molecule expression and synthesis of mediators that are probably important in immune and inflammatory reactions involving the nervous system and in cerebral tissue repair. The response of astrocytes to interferon-gamma mainly resulted in increased expression of major histocompatibility complex antigens and co-stimulatory molecules (intercellular adhesion molecule-1, LFA-1 alpha) which mediate astrocyte-T-cell interactions. Another co-stimulatory molecule, B7, was neither expressed nor inducible by IFN-gamma and other cytokines. TNF-alpha and IL-1 beta were more efficient in stimulating synthesis of immunoregulatory and proinflammatory cytokines (IL-6, IL-8 and colony-stimulating factors), cytokine antagonists (TNF-alpha soluble receptors), or cytokines with a possible neuroprotective role (leukemia inhibitory factor); they also increased expression of some co-stimulatory molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1). Transforming growth factor-beta 1 was a strong inducer of leukemia inhibitory factor, but did not affect either major histocompatibility complex/co-stimulatory molecule expression or cytokine synthesis. Thus, different cytokines activate distinct functional programs in astrocytes, which may play a specific role in different brain diseases or at different stages of the same disease. It was additionally observed that the response of human astrocytes to cytokines (in particular the inducible synthesis of certain cytokines) varied greatly depending on the presence or absence of neurons in the culture system. This finding suggests that neuronal-glial interactions may be implicated in determining the activation threshold of astrocytes to inflammatory cytokines.
星形胶质细胞参与中枢神经系统病理生理学过程可能涉及细胞因子，细胞因子既是星形胶质细胞功能的刺激物，也是其介导物。我们使用高度纯化的人星形胶质细胞培养物作为实验工具，来研究细胞因子对黏附分子表达以及对可能在涉及神经系统的免疫和炎症反应及脑组织修复中起重要作用的介质合成的影响。星形胶质细胞对γ干扰素的反应主要导致主要组织相容性复合体抗原和共刺激分子（细胞间黏附分子-1、淋巴细胞功能相关抗原-1α）表达增加，这些分子介导星形胶质细胞与T细胞的相互作用。另一种共刺激分子B7既不表达，也不能被γ干扰素和其他细胞因子诱导。肿瘤坏死因子-α和白细胞介素-1β在刺激免疫调节和促炎细胞因子（白细胞介素-6、白细胞介素-8和集落刺激因子）、细胞因子拮抗剂（肿瘤坏死因子-α可溶性受体）或可能具有神经保护作用的细胞因子（白血病抑制因子）的合成方面更有效；它们还增加了一些共刺激分子（细胞间黏附分子-1和血管细胞黏附分子-1）的表达。转化生长因子-β1是白血病抑制因子的强诱导剂，但不影响主要组织相容性复合体/共刺激分子的表达或细胞因子的合成。因此，不同的细胞因子激活星形胶质细胞中不同的功能程序，这可能在不同的脑部疾病或同一疾病的不同阶段发挥特定作用。此外还观察到，人星形胶质细胞对细胞因子的反应（特别是某些细胞因子的诱导合成）因培养系统中是否存在神经元而有很大差异。这一发现表明，神经元与胶质细胞的相互作用可能参与决定星形胶质细胞对炎性细胞因子的激活阈值。
