AUTOCRINE AND PARACRINE REGULATION OF ASTROCYTE FUNCTION BY TRANSFORMING GROWTH-FACTOR-BETA

Recent evidence indicates that astrocytes have a wide range of functions, usually attributed to cells of the immune system, which are critical for maintaining a balanced homeostatic environment in the central nervous system (CNS). Moreover, these cells are known to participate in inflammatory events within the CNS by secreting cytokines such as transforming growth factor-beta (TGF-beta). In this study we have investigated the ability of TGF-beta to influence astrocyte functions. TGF-beta-1 mRNA is constitutively expressed by astrocytes in vitro, and when cultures are stimulated with exogenous TGF-beta-1 an increase in the expression of this mRNA can be shown, suggesting both autocrine and paracrine regulation. In in vitro assays, TGF-beta-1 is chemotactic for astrocytes in a dose-dependent fashion and inhibits astrocyte proliferation. These results indicating signal transduction by TGF-beta-1-prompted studies to explore receptor-ligand interactions on isolated astrocyte populations. In a receptor binding assay, we demonstrate that astrocytes appear to express three distinct TGF-beta receptor subtypes with nearly 10000 receptors per cell. Thus, TGF-beta may play an important role in regulating astrocyte functions pivotal to the evolution of intracerebral immune responses including recruitment and activation of glial cells at local inflammatory sites within the CNS.