Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Phosphatidylinositol 4-phosphate 5-kinase ${\alpha}$ is induced in ganglioside-stimulated brain astrocytes and contributes to inflammatory responses

  • Lee, Sang-Yoon (Neuroscience Graduate Program Ajou University School of Medicine) ;
  • Kim, Bo-Kyung (Neuroscience Graduate Program Ajou University School of Medicine) ;
  • Yoon, Sa-Rah (Department of Microbiology Ajou University School of Medicine) ;
  • Kim, Yeon-Joo (Chronic Inflammatory Disease Research Center Ajou University School of Medicine) ;
  • Liu, Tian (Neuroscience Graduate Program Ajou University School of Medicine) ;
  • Woo, Joo-Hong (Chronic Inflammatory Disease Research Center Ajou University School of Medicine) ;
  • Chwae, Yong-Joon (Department of Microbiology Ajou University School of Medicine) ;
  • Joe, Eun-Hye (Neuroscience Graduate Program Ajou University School of Medicine) ;
  • Jou, Il-O (Chronic Inflammatory Disease Research Center Ajou University School of Medicine)
  • Accepted : 2010.08.18
  • Published : 2010.09.30
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Abstract

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 ${\alpha}$ ($PIP5K{\alpha}$) that is responsible for production of phosphatidylinositol 4,5-bisphosphate ($PI[4,5]P_2$) regulates many important cell functions at the cell surface. Here, we have examined whether $PIP5K{\alpha}$ 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 $PIP5K{\alpha}$ mRNA and protein expression levels. $PI(4,5)P_2$ imaging using a fluorescent tubby (R332H) expression as a $PI(4,5)P_2$-specific probe showed that ganglioside treatment increased $PI(4,5)P_2$ level. Interestingly, microRNA-based $PIP5K{\alpha}$ knockdown strongly reduced ganglioside-induced transcription of proinflammatory cytokines IL-$1{\beta}$ and $TNF{\alpha}$. $PIP5K{\alpha}$ knockdown also suppressed ganglioside-induced phosphorylation and nuclear translocation of NF-${\kappa}B$ and the degradation of $l{\kappa}B-{\alpha}$, indicating that $PIP5K{\alpha}$ knockdown interfered with the ganglioside-activated NF-${\kappa}B$ signaling. Together, these results suggest that $PIP5K{\alpha}$ is a novel inflammatory mediator that undergoes upregulation and contributes to immune responses by facilitating NF-${\kappa}B$ activation in ganglioside-stimulated astrocytes.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation, Chronic Inflammatory Disease Research Center at Ajou University, Korea Research Foundation, Ajou University School of Medicine

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