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.
