Monokine modulation of human astroglial cell production of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. I. Effects of IL-1 alpha and IL-beta.
Granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF enhance phagocyte survival and function and are produced by fibroblasts and endothelial cells after induction by inflammatory mediators such as IL-1. Our ability to detect G-CSF and GM-CSF activity in the conditioned medium of the human astroglial tumor cell line, U87MG, and molecularly clone the cDNA for G-CSF from a U87MG cDNA library raised the possibility that astroglial cells are capable of G-CSF and GM-CSF production within the central nervous system; if so, the production of these CSF by astroglial cells may be inducible by IL-1. We examined the effects of IL-1 alpha and IL-1 beta on the production of G-CSF and GM-CSF by U87MG and U373MG, another astroglial tumor cell line that does not constitutively produce CSF. We demonstrate that both U87MG and U373MG can be induced to produce G-CSF and GM-CSF by exposure to IL-1 alpha and IL-1 beta. This response, measured by accumulation of increased CSF mRNA, is rapid, sensitive and due to the enhanced stability of CSF message following IL-1 exposure. The implications of these findings to the immunopathogenesis of central nervous system infections are discussed.
Department of Medicine, University of Pittsburgh School of Medicine, PA.
D J
DJ
Tweardy
P L
PL
Mott
E W
EW
Glazer
D001254:Astrocytoma / Q000378:metabolism*; D015152:Blotting, Northern; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor