IL-1Beta Actions on CNS Neurons and Astrocytes

白介素- 1b （interleukin - 1b, IL-1B）是一种由脑胶质细胞产生的多效性细胞因子，影响多种不同的细胞类型。当IL-1B与胶质细胞上的受体相互作用时，它激活一个特定的细胞内信号级联，诱导许多生长因子和细胞因子的产生。大脑中特定的神经元群，特别是海马神经元，也有IL-1B的受体，但是神经元不产生细胞因子和生长因子来响应IL-1B。该细胞因子激活的不同信号转导途径决定了不同细胞类型的功能反应。因此，在这些研究中，我们将阐明与星形胶质细胞相比，介导IL-1B在神经元中的作用的不同信号通路。此外，IL-1B在胶质细胞中诱导的生长因子之一是神经生长因子（NGF）。神经胶质细胞中的一种NGF受体（p75）也可由IL-1B诱导，这表明NGF对神经胶质细胞的作用不同于其对神经元的典型神经营养作用。这些研究将探讨神经生长因子对神经胶质细胞的信号通路和功能影响。生长因子和细胞因子影响许多不同的细胞群，但诱导不同的细胞类型特异性反应。阐明多效性细胞因子如IL-1B在神经元和胶质细胞中激活的信号转导通路，将有助于深入了解单一因子如何在不同细胞类型中激活不同的信号事件和功能后果。

0078210Friedman, W.Interleukin-1B (IL-1B) is a potent and pleiotropic cytokine produced by glia in the brain which influences many different cell types. When IL-1B interacts with receptors on glia, it activates a specific intracellular signaling cascade inducing production of many growth factors and cytokines. Specific neuronal populations in the brain, in particular hippocampal neurons, also have receptors for IL-1B, however neurons do not produce cytokines and growth factors in response to IL-1B. The distinct signal transduction pathways activated by this cytokine determine the functional response of different cell types. In these studies, therefore, we will elucidate the different signaling pathways that mediate the actions of IL-1B in neurons compared to astrocytes. In addition, one of the growth factors which is induced by IL-1B in glia is nerve growth factor (NGF). One of the NGF receptors (p75) is also induced by IL-1B in glial cells, suggesting that NGF has effects on glia distinct from its well-characteristic neurotrophic effects on neurons. These studies will investigate the signaling pathways and functional consequences of NGF on glial cells.Growth factors and cytokines influence many different cell populations, but induce distinct responses which are cell type-specific. Elucidation of the signal transduction pathways activated in neurons and glia by a pleiotropic cytokine such as IL-1B will allow insight into how a single factor can activate different signaling events and functional consequences in distinct cell types.