Modulation of microglia by stem cell factor

✍ Scribed by Su-Chun Zhang; Sergey Fedoroff

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 153 KB
• Volume: 53
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19980701)53:1<29::aid-jnr4>3.0.co;2-l

✦ Synopsis

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 processbearing 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-␣), and interleukin-1␤ (IL-1␤). SCF potentiates lipopolysaccharide-stimulated, but attenuates interferon-␥ TFN␣ mediated expression of the mRNAs of IL-1␤ and TNF-␣. The SCF-induced expression of neurotrophin mRNAs is enhanced by the addition of lipopolysaccharide (LPS) but is reduced by IFN␥. The interactions between SCF and LPS or IFN␥ in the regulation of inflammationassociated 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.