Abstract
We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferentially in human fetal astrocytes in an age-dependent manner. Astrocytes from 5-week-old brains showed high proliferation and reduced survival, whereas 10-week-old astrocytes exhibited opposite effects. These effects were suppressed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by recombinant RANTES. RANTES induced tyrosine phosphorylation of several cellular proteins and nuclear translocation of STAT-1 in astrocytes. Interferon-gamma (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gamma and only 10-week-old astrocytes expressed the IFN-gamma receptor. Blocking of IFN-gamma with antibody reversed the effects of RANTES, indicating that cytokine/chemokine networks are critically involved in brain development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology
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Astrocytes / physiology*
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Cell Cycle / physiology
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Cell Survival
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Cells, Cultured
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Chemokine CCL5 / genetics
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Chemokine CCL5 / metabolism*
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DNA-Binding Proteins / metabolism
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Embryo, Mammalian / cytology
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Female
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Humans
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Immunoblotting
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Immunohistochemistry
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In Situ Hybridization
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Interferon-gamma / metabolism*
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Interleukin-8 / genetics
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Interleukin-8 / metabolism*
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Mice
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Mice, Inbred C57BL
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Phosphorylation
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Pregnancy
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Pregnancy Trimester, First
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Prosencephalon / cytology
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Prosencephalon / embryology*
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Prosencephalon / metabolism
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RNA, Messenger / metabolism
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Receptors, CCR5 / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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STAT1 Transcription Factor
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Trans-Activators / metabolism
Substances
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Chemokine CCL5
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DNA-Binding Proteins
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Interleukin-8
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RNA, Messenger
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Receptors, CCR5
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Recombinant Proteins
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STAT1 Transcription Factor
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STAT1 protein, human
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Stat1 protein, mouse
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Trans-Activators
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Interferon-gamma