title: RANTES promotes growth and survival of human first-trimester forebrain astrocytes.
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.
authors.affiliation: Karolinska Institutet, Department of Medicine, Centre for Infectious Medicine, Huddinge University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bakhiet
authors.forename: A
authors.initials: A
authors.lastname: Tjernlund
authors.forename: A
authors.initials: A
authors.lastname: Mousa
authors.forename: A
authors.initials: A
authors.lastname: Gad
authors.forename: S
authors.initials: S
authors.lastname: Strömblad
authors.forename: W A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: A
authors.initials: A
authors.lastname: Seiger
authors.forename: J
authors.initials: J
authors.lastname: Andersson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D018946:Chemokine CCL5; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D012333:RNA, Messenger; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma