DIFFERENTIAL REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA-1 GENE-EXPRESSION BY GLUCOCORTICOIDS IN HUMAN T-CELLS AND GLIAL-CELLS

The inflammatory process in the brain requires bidirectional interacti on of the immune and nervous systems, Evidently, astrocytic glial cell s play an important role in facilitating this communication by releasi ng immunomodulators and cytokines. Expression of transforming growth f actor beta-1 (TGF beta-1), a potent inhibitor of T cell function and g lial cell proliferation, is highly regulated in T cells and is believe d to be an important component in the molecular interaction between th e immune and nervous systems. Comparative analysis of TGF beta-1 gene expression in human T and glial cells by Northern hybridization and S1 nuclease protection assay showed that dexamethasone (DM) caused a sig nificant decrease in the basal and PMA-induced levels of TGF beta-1 mR NA in glial cells but not in T cells. This reduction correlated with a lower level of TGF beta-1 protein production. Transient transfection assay rising deletion constructs of the 5' TGF beta-1 gene promoter-co ntaining sequences between -453 and +11 bp identified a region spannin g -160 to -60 bp as a potential sequence responsive to regulation by D M in T cells, whereas in glial cells, the overall transcriptional acti vity of the 5' TGF beta-1 promoter was reduced after DM treatment, but promoter activity within each construct remained constant in response to DM. Thus, a DM-responsive region could not be identified within th e TGF beta-1 promoter in glial cells, These findings suggest that TGF beta-1 gene expression is differentially regulated by distinct regulat ory elements in T and glial cells, and that extracellular stimulators, including glucocorticoids, can utilize the TGF beta-1-regulatory path way to affect the functions of neural and immune cells.