Role of calmodulin in the differentiation/activation of microglial cells.
In the present work the role of calmodulin (CaM) in regulating lipopolysaccharide (LPS)-induced microglial activation and in the spontaneous microglial differentiation has been investigated. We used pure rat microglial cell cultures to examine the effects of W13, a specific inhibitor of CaM, on microglial activation produced by LPS and the effect of CaM inhibition on microglial proliferation induced by the macrophage colony-stimulating factor (M-CSF). Microglial morphological transformation, inducible nitric oxide synthase (iNOS) activity and proliferating cell nuclear antigen (PCNA) immunostaining were determinate. Results show that CaM does not participate in the microglial increase of iNOS produced by LPS. In contrast, it is involved in spontaneous microglial ramification and in the activation of proliferation from quiescence. Multiple second-messenger pathways are involved in the transduction of signals initiated by LPS. The study of these mechanisms may allow us to extend our knowledge of the signals controlling the expression of these mediators.
Casal
C
C
Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, C/Rosselló 161, 6ena planta, E-08036, Barcelona, Spain.
Tusell
J M
JM
Serratosa
J
J
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D017628:Microglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008940:Mitotic Index; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D008070:Lipopolysaccharides; D009573:Nitrites; D018809:Proliferating Cell Nuclear Antigen; D013449:Sulfonamides; C040184:W 12; D016173:Macrophage Colony-Stimulating Factor; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat