Regulation of TNF - alpha Gene Expression in Human Fetal Astrocytes

ABSTRACT

Tumor necrosis factor-n (TNF - alpha) involved in the pathogenesis of multiple sclerosis and contribute to the degeneration of oligodendrocytes as well as neurons. TNF - alpha is produced by miocroglia and astrocytes, which also produce hormones and cytokines that influence its biological activity. Astrocytes, the major glial cells in the CNS, are capable of producing TNF - alpha at both the mRNA and protein levels in response to interleukine-1 (IL-1) or TNF - alpha. Two immunosuppressive cytokines, transforming growth factor - beta (TGF - beta) and IL-10, have been shown to influence glial cell function. TGF - beta can modulate the activity of glial cells by inhibiting interferon-gamma (IFN - gamma) induced expression of class II major histocompatibility complex (MHC) molecules on astrocytes and microglia. To explore the role of astrocytes in the production of TNF - alpha, astrocytes were pretreated with IL-10 or TGF - beta and then stimulated with IL-1p to determine their effects on TNF - alpha production. The secretion of TNF - alpha by human fetal astrocytes was markedly inhibited by TGF - beta at a low concentration. In contrast IL-10 had no effect on TNF - alpha mRNA level. These results show that TGF - beta may regulate the expression of TNF - alpha in activated human fetal astrocytes.