Interferon-gamma produced by encephalitogenic cells induces suppressors of cytokine signaling in primary murine astrocytes

Suppressors of cytokine signaling (SOCS) are proteins that modulate cytokine responses in lymphoid cells. In these studies, cultured primary mouse astrocytes expressed SOCS-3 mRNA constitutively. Treatment with interferon-gamma (IFN-g) induced SOCS-1 and enhanced SOCS-3 expression, and was associated with decreased tumor necrosis factor-alpha (TNF) and increased leukemia inhibitory factor (LIF) in culture supernatants. Treatment with conditioned medium from myelin basic protein-stimulated encephalitogenic lymphoid cells (MBP-CM) increased SOCS-3 and induced SOCS-1 expression. The effects were largely due to IFN-g in MBP-CM, as anti-IFN-g antibody diminished induction. These findings suggest a role for IFN-g-induced SOCS expression in regulation of CNS inflammatory responses by astrocytes.