RRC ID 45266
Author Yu Z, Ono C, Aiba S, Kikuchi Y, Sora I, Matsuoka H, Tomita H.
Title Therapeutic concentration of lithium stimulates complement C3 production in dendritic cells and microglia via GSK-3 inhibition.
Journal Glia
Abstract Evidence indicates that widely prescribed mood stabilizer, lithium (Li), mediates cellular functions of differentiated monocytic cells, including microglial migration, monocyte-derived dendritic cell (MoDC) differentiation, and amelioration of monocytic malfunctions observed in neuropsychiatric diseases. Here, we surveyed molecules which take major roles in regulating these monocytic cellular functions. MoDCs treated with 1 and 5 mM Li, and microglia separated from Li-treated mice were subjected to microarray-based comprehensive gene expression analyses. Findings were validated using multiple experiments, including quantitative PCR, ELISA and immunostaining studies. Differing effects of Li on the two cell types were observed. Inflammation- and chemotaxis-relevant genes were significantly over-represented among Li-induced genes in MoDCs, whereas no specific category of genes was over-represented in microglia. The third component of complement (C3) was the only gene which was significantly induced by a therapeutic concentration of Li in both MoDCs and microglia. C3 production was increased by Li via GSK-3 inhibition. Li-induced C3 production was seen only in differentiated monocytic cells, but not in circulating monocytes. Our findings highlight a link between Li treatment and C3 production in differentiated monocytic cells, and reveal a regulatory role of GSK-3 in C3 production. Induction of microglial C3 production might be a novel neuroprotective mechanism of Li via regulating interactions between microglia and neurons. GLIA 2015;63:257-270.
Volume 63(2)
Pages 257-70
Published 2015-2
DOI 10.1002/glia.22749
PMID 25179772
MeSH Analysis of Variance Animals Cell Differentiation / drug effects Cells, Cultured Complement C3 / metabolism* Dendritic Cells / drug effects* Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Enzyme-Linked Immunosorbent Assay Gene Expression Regulation / drug effects Glycogen Synthase Kinase 3 / metabolism* Humans Lithium / pharmacology* Mice Mice, Inbred C57BL Microarray Analysis Microglia / drug effects* Monocytes / drug effects Phagocytosis / drug effects
IF 5.846
Times Cited 4
Human and Animal Cells