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.

Transforming growth factor alpha acts as a gliatrophin for mouse and human astrocytes

“…In mammals, astrocyte death contributes to various pathological events (Takuma et al, 2004;Giffard and Swanson, 2005), and regulation of astrocytes numbers through developmental death has been documented (Soriano et al, 1993;Krueger et al, 1995). Nevertheless, only scarce studies have been devoted to the identification of growth factors capable of promoting the survival of these glial cells (Yokoyama et al, 1993;Bakhiet et al, 2001;Saas et al, 2002). In contrast, several studies point to products of neuregulin1 gene, a member of the EGF family, as survival factors during the development of both Schwann cells (Lemke, 2001) and oligodendrocytes (Fernandez et al, 2000).…”

Oncogenic H-Ras V12 promotes anchorage-independent cytokinesis in human fibroblasts

“…Cells were fixed in 70% EtOH, and the cell cycle distribution was determined by using anti-BrdU mAb G3G4 (Developmental Studies Hybridoma Bank, Department of Biological Sciences, University of Iowa, Iowa City, IA) and propidium iodide double-staining, followed by flow cytometry as described in ref. 36. For cytostaining, attached cells were trypsinized, and all cells were attached to glass slides by cytospin before staining.…”

Retinoblastoma Susceptibility Gene Product (pRb) and p107 Functionally Separate the Requirements for Serum and Anchorage in the Cell Cycle G1-phase

“…To monitor the time of S-phase entry, G 0 -released cells were harvested at different time points after release and fixed as above. The cell cycle distribution was determined by using anti-BrdUrd mAb G3G4 (Developmental Studies Hybridoma Bank, Department of Biological Sciences, University of Iowa, IA) and propidium iodide double-staining, followed by flow cytometry analysis as described previously (22). To facilitate comparisons between different experiments and cell types, values of cell proliferation after depletion of serum or anchorage were calculated as the percentage of cells dependent on serum and anchorage to enter S-phase within 30 h. A portion of MEFs deficient in pRb and p107 grew independently of both serum and adhesion, which is consistent with our previous observations (23).…”