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

Chemokines are secreted proteins that function as chemoattractants, mediati ng the recruitment of specific subsets of leukocytes to sites of tissue dam age and immunological reactions. Chemokines may also function as antiviral agents, since viruses such as human immunodeficiency virus type 1 (HIV-1) u se chemokine receptors as co-receptors for viral entry. This study examines whether virus-induced interferon, IFN beta, or immune-related interferon, IFN gamma, affects the production of beta-chemokines by CNS microglia and p eripheral monocytes. When IFN beta was used as the stimulus, induction of M IP-1 alpha, MIP-l beta, MCP-1, and RANTES mRNA and protein was observed wit hin 12 h of stimulation in microglia. By contrast, when IFN gamma was used as the stimulus, only IMCP-1 was induced. IFN beta stimulation of blood mon ocytes resulted in upregulation of MIP-alpha, MIP-1 beta, and MCP-1. Thus, type I and II interferons differentially regulate beta-chemokines in human fetal microglia and peripheral blood monocytes. These observations may have relevance for the therapeutic activity of IFN beta in multiple sclerosis a nd for the antiviral effects of IFN beta for HIV-1 infection of monocytes a nd microglia. (C) 2000 Wiley-Liss, Inc.