Modulation of microglia by stem cell factor.
We reported previously that stem cell factor (SCF) is produced mainly by neurons and that its receptor (c-kitR), encoded by the protooncogene c-kit, is expressed in microglia, suggesting that SCF/c-kitR signaling may be involved in neuron-microglia interactions. We now report that SCF supports microglial survival in cultures, maintains them in process-bearing morphology, and inhibits microglial proliferation induced by colony stimulating factor-1. SCF potentiates microglial expression of the mRNAs of nerve growth factor, brain-derived neurotrophic factor and ciliary neurotrophic factor, and downregulates microglial expression of the inflammation-associated cytokines, tumor necrosis factor-a (TNF-alpha), and interleukin-1beta (IL-1beta). SCF potentiates lipopolysaccharide-stimulated, but attenuates interferon-gamma TFNalpha mediated expression of the mRNAs of IL-1beta and TNF-alpha. The SCF-induced expression of neurotrophin mRNAs is enhanced by the addition of lipopolysaccharide (LPS) but is reduced by IFNgamma. The interactions between SCF and LPS or IFNgamma in the regulation of inflammation-associated cytokine gene expression are accompanied by the differential regulation of c-kitR in microglia. These observations suggest that SCF/c-kitR signaling modulates microglial activity.
Zhang
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SC
Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Fedoroff
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S
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D019089:Stem Cell Factor / Q000494:pharmacology*
D016207:Cytokines; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit