KMID : 0620920100420090662
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Experimental & Molecular Medicine 2010 Volume.42 No. 9 p.662 ~ p.673
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Phosphatidylinositol 4-phosphate 5-kinase ¥á is induced in ganglioside-stimulated brain astrocytes and contributes to inflammatory responses
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Lee Sang-Yoon
Kim Bo-Kyung Yoon Sa-Rah Kim Yeon-Joo Liu Tian Woo Joo-Hong Chwae Yong-Joon Joe Eun-Hye Jou Ilo
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Abstract
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In brain tissue, astrocytes play defensive roles in central nervous system integrity by mediating immune responses against pathological conditions. Type I phosphatidylinositol 4-phosphate 5-kinase ¥á (PIP5K¥á) that is responsible for production of phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) regulates many important cell functions at the cell surface. Here, we have examined whether PIP5K¥á is associated with astrocyte inflammatory responses. Gangliosides are releasable from damaged cell membranes of neurons and capable of inducing inflammatory responses. We found that treatment of primary cultured astrocytes with gangliosides significantly enhanced PIP5K¥á mRNA and protein expression levels. PI(4,5)P2 imaging using a fluorescent tubby (R332H) expression as a PI(4,5)P2-specific probe showed that ganglioside treatment increased PI(4,5)P2 level. Interestingly, microRNA-based PIP5K¥á knockdown strongly reduced ganglioside-induced transcription of proinflammatory cytokines IL-1¥â and TNF¥á. PIP5K¥á knockdown also suppressed ganglioside-induced phosphorylation and nuclear translocation of NF-¥êB and the degradation of I¥êB-¥á, indicating that PIP5K¥á knockdown interfered with the ganglioside-activated NF-¥êB signaling. Together, these results suggest that PIP5K¥á is a novel inflammatory mediator that undergoes upregulation and contributes to immune responses by facilitating NF-¥êB activation in ganglioside-stimulated astrocytes.
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KEYWORD
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astrocytes, brain, gangliosides, inflammation, NF-¥êB, 1-phosphatidylinositol-4-phosphate 5-kinase
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