Greer Murphy M.D., Ph.D.

Publication Details

  • Overexpression of macrophage colony-stimulating factor receptor on microglial cells induces an inflammatory response JOURNAL OF BIOLOGICAL CHEMISTRY Mitrasinovic, O. M., Perez, G. V., Zhao, F. F., Lee, Y. L., Poon, C., Murphy, G. M. 2001; 276 (32): 30142-30149

    Abstract:

    Microglia are important in the inflammatory response in Alzheimer's disease (AD). We showed previously that macrophage colony-stimulating factor receptor (M-CSFR), encoded by the c-fms protooncogene, is overexpressed on microglia surrounding amyloid beta (Abeta) deposits in the APP(V717F) mouse model for AD. The M-CSFR is also increased on microglia after experimental brain injury and in AD. To determine the relevance of these findings, we transiently expressed M-CSFR on murine BV-2 and human SV-A3 microglial cell lines using an SV40-promoted c-fms construct. M-CSFR overexpression resulted in microglial proliferation and increased expression of inducible nitric-oxide synthase, the proinflammatory cytokines interleukin-1alpha, macrophage inflammatory protein 1-alpha, and interleukin-6 and of macrophage colony-stimulating factor (M-CSF) itself. Antibody neutralization of M-CSF showed that the M-CSFR-induced proinflammatory response was dependent on M-CSF in the culture media. By using a co-culture of c-fms-transfected murine microglia and rat organotypic hippocampal slices and a species-specific real time reverse transcriptase-polymerase chain reaction assay and enzyme-linked immunosorbent assay, we showed that M-CSFR overexpression on exogenous microglia induced expression of interleukin-1alpha by the organotypic culture. These results show that increased M-CSFR expression induces microglial proliferation, cytokine expression, and a paracrine inflammatory response, suggesting that in APP(V717F) mice increased M-CSFR on microglia could be an important factor in Abeta-induced inflammatory response.

    View details for Web of Science ID 000170558000073

    View details for PubMedID 11387343

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