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, IFNbeta, or immune-related interferon, IFNgamma, affects the production of beta-chemokines by CNS microglia and peripheral monocytes. When IFNbeta was used as the stimulus, induction of MIP-1alpha, MIP-1beta, MCP-1, and RANTES mRNA and protein was observed within 12 h of stimulation in microglia. By contrast, when IFNgamma was used as the stimulus, only MCP-1 was induced. IFNbeta stimulation of blood monocytes resulted in upregulation of MIP-1alpha, MIP-1beta, 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 IFNbeta in multiple sclerosis and for the antiviral effects of IFNbeta for HIV-1 infection of monocytes and microglia.
McManus
C M
CM
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Liu
J S
JS
Hahn
M T
MT
Hua
L L
LL
Brosnan
C F
CF
Berman
J W
JW
Lee
S C
SC
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D005333:Fetus; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D007370:Interferon Type I; D019402:Macrophage Inflammatory Proteins; D007371:Interferon-gamma