Transforming growth factor-beta 1 differentially regulates proliferation and MHC class-II antigen expression in...

To facilitate investigation of cytokine regulation of reactive astrogliosis, primary astrocyte cultures from neonatal murine forebrain and brainstem were established. Forebrain and brainstem astrocytes proliferated at a similar rate under basal culture conditions, and both were growth-inhibited by treatment with recombinant murine interferon-gamma. The growth of cultured brainstem astrocytes was significantly enhanced by exposure to recombinant human transforming growth factor-beta 1. In contrast, proliferation of forebrain astrocytes was not significantly affected by transforming growth factor-beta 1. The disparate responses of brainstem and forebrain astrocytes to transforming growth factor-beta 1 treatment were not limited to effects on cell growth, since transforming growth factor-beta 1 could block interferon-gamma-induced MHC class-II antigen expression on cultured brainstem astrocytes but not on forebrain cells. Results could not be attributed to use of an heterologous cytokine/cellular target system, since similar variability in transforming growth factor-beta 1 modulation of major histocompatibility complex antigen expression could be demonstrated using two human astrocytoma cell lines. This report is the first to document mitogenic response to transforming growth factor-beta 1 for neuroepithelial cells. The role of transforming growth factor-beta 1 in regulating aspects of reactive astrogliosis, particularly in the context of inflammatory demyelination, requires further investigation. Furthermore, these studies may provide insight into regional variability in the sequelae of inflammation within the central nervous system.