RANTES promotes growth and survival of human first-trimester forebrain astrocytes |
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Authors: | Bakhiet M Tjernlund A Mousa A Gad A Strömblad S Kuziel W A Seiger A Andersson J |
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Institution: | Karolinska Institutet, Department of Medicine, Centre for Infectious Medicine, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. |
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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. |
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