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Enhanced phosphatidylinositol 4-phosphate 5-kinase alpha expression and PI(4,5)P2 production in LPS-stimulated microglia.

Lee, SY; Kim, B; Jeong, HK; Min, KJ; Liu, T; Park, JY; Joe, EH; Jou, I
Neurochemistry international, 57(5):600-607, 2010
Journal Title
Neurochemistry international
Microglia are the major glial cells responsible for immune responses against harmful substances in the central nervous system. Type I phosphatidylinositol 4-phosphate 5-kinase alpha (PIP5Kalpha) and its lipid product, phosphatidylinositol 4,5-bisphosphate (PI[4,5]P(2)), regulate important cell surface functions. Here, we report that lipopolysaccharide (LPS) significantly enhanced PIP5Kalpha mRNA and protein expression levels in a time- and concentration-dependent manner in microglia. Furthermore, LPS stimulation led to a robust increase in PI(4,5)P(2) in the plasma membrane, demonstrated by PI(4,5)P(2) immunostaining or PI(4,5)P(2) imaging using a PI(4,5)P(2)-specific probe, tubby (R332H), fused to yellow fluorescent protein. Phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, and c-Jun N-terminal kinase signaling pathway inhibitors clearly reduced PIP5Kalpha expression, indicating that these pathways are necessary for LPS-induced PIP5Kalpha expression. In addition, inhibition of nuclear factor-kappaB and Sp1 transcription factors interfered with the LPS-induced upregulation of PIP5Kalpha. Delivery of PI(4,5)P(2) into microglia increased the expression of interleukin-1beta and tumor necrosis factor alpha. These findings indicate that PIP5Kalpha upregulation and the subsequent rise in PI(4,5)P(2) in LPS-stimulated microglia may positively regulate microglial inflammatory responses.
MeSH terms
AnimalsBlotting, WesternCell LineCytokines/biosynthesisFluorescent Antibody TechniqueLipopolysaccharides/*pharmacologyMacrophage Activation/drug effectsMiceMicroglia/drug effects/immunology/*metabolismMicroscopy, ConfocalNF-kappa B/biosynthesisPhosphatidylinositol 4,5-Diphosphate/*biosynthesisPhosphotransferases (Alcohol Group Acceptor)/*biosynthesisReverse Transcriptase Polymerase Chain ReactionStimulation, ChemicalTransfection
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Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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