Differential induction of chemokines in human microglia by type I and II interferons

Chemokines are secreted proteins that function as chemoattractants, mediating the recruitment of specific subsets of leukocytes to sites of tissue damage and immunological reactions. Chemokines may also function as antiviral agents, since viruses such as human immunodeficiency virus type 1 (HIV-1) use chemokine receptors as co-receptors for viral entry. This study examines whether virus-induced interferon, IFNβ, or immune-related interferon, IFNγ, affects the production of β-chemokines by CNS microglia and peripheral monocytes. When IFNβ was used as the stimulus, induction of MIP-1α, MIP-1β, MCP-1, and RANTES mRNA and protein was observed within 12 h of stimulation in microgila. By contrast, when IFNγ was used as the stimulus, only MCP-1 was induced. IFNβ stimulation of blood monocytes resulted in upregulation of MIP-1α, MIP-1β, and MCP-1. Thus, type I and II interferons differentially regulate β-chemokines in human fetal microglia and peripheral blood monocytes. These observations may have relevance for the therapeutic activity of IFNβ in multiple sclerosis and for the antiviral effects of IFNβ for HIV-1 infection of monocytes and microglia. (C) 2000 Wiley-Liss, Inc.