Protein kinase C and phosphoinositol-3-kinase mediate differentiation or proliferation of slice-derived rat microglia.

Granulocyte-macrophage colony-stimulating factor plays an important role in the activation of microglia in the central nervous system. We have recently shown (see text) that granulocyte-macrophage colony-stimulating factor activates the proliferation and subsequent migration of microglia from organotypic cortex brain slices. The aim of this study was to investigate whether this activation is modulated by different putative intracellular pathway inhibitors. Our data show that the protein kinase C inhibitor staurosporine enhanced the proliferation as well as the differentiation of slice-derived microglia, while the phosphoinositol-3-kinase inhibitor LY294002 markedly suppressed the proliferative activity. In conclusion, proliferation, migration, as well as differentiation of rat microglia are highly regulated by intracellular signaling cascades. Copyright 2003 S. Karger AG, Basel