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.
Zassler
Birgit
B
Laboratory of Psychiatry, Department of Psychiatry, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Schermer
Christine
C
Humpel
Christian
C
D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D017628:Microglia / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D009000:Monocytes / Q000276:immunology; D009025:Morpholines / Q000494:pharmacology; D009924:Organ Culture Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology
D039481:CD11b Antigen; D002867:Chromones; D004791:Enzyme Inhibitors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D019311:Staurosporine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one