The astrocyte mitogen, tumor necrosis factor-alpha, inhibits the proliferative effect of more potent adult human astrocyte mitogens, gamma-interferon and activated T-lymphocyte supernatants.
The proliferative response of adult human astrocytes to tumor necrosis factor-alpha (TNF-alpha) was examined. Applied alone, TNF-alpha was dependent on the content of serum in the feeding medium, being mitogenic only in conditions of over 15% serum in medium. In accordance with previous results, supernatants from activated human CD8+ T-lymphocytes (CD8 SN) and recombinant human interferon-gamma (IFN-gamma) enhanced proliferation of adult human astrocytes in 5% serum-containing medium. Simultaneous administration of TNF-alpha (10-1000 units), however, abrogated the mitogenic effects of either CD8 SN or IFN-gamma; the inhibitory effect of TNF-alpha was lost if applied 2 days following IFN-gamma treatment. These studies show that while TNF-alpha is an astrocyte mitogen under selected conditions, it inhibits proliferation induced by other mitogens. In this manner, TNF-alpha may be important in regulating the proliferative response of astrocytes during reactive astrogliosis in vivo.
Tejada-Berges
T
T
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Que., Canada.
Yong
V W
VW
D000328:Adult; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D001769:Blood; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003470:Culture Media; D007375:Interleukin-1; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma