Phosphatidylinositol 4-phosphate 5-kinase alpha is induced in ganglioside-stimulated brain astrocytes and contributes to inflammatory responses.
10.3858/emm.2010.42.9.066
- Author:
Sang Yoon LEE
1
;
Bokyung KIM
;
Sarah YOON
;
Yeon Joo KIM
;
Tian LIU
;
Joo Hong WOO
;
Yong Joon CHWAE
;
Eun hye JOE
;
Ilo JOU
Author Information
1. Neuroscience Graduate Program, Ajou University School of Medicine Suwon 443-721, Korea. sangyoon@ajou.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
astrocytes;
brain;
gangliosides;
inflammation;
NF-kappaB;
1-phosphatidylinositol-4-phosphate 5-kinase
- MeSH:
Animals;
Astrocytes/*metabolism;
Cells, Cultured;
Gangliosides/*metabolism;
Gene Knockdown Techniques;
Inflammation/*metabolism;
Interleukin-1/metabolism;
NF-kappa B/metabolism;
Phosphotransferases (Alcohol Group Acceptor)/*metabolism;
RNA, Messenger/*genetics/metabolism;
Rats;
Rats, Sprague-Dawley;
Signal Transduction;
Tumor Necrosis Factor-alpha/metabolism;
Up-Regulation
- From:Experimental & Molecular Medicine
2010;42(9):662-673
- CountryRepublic of Korea
- Language:English
-
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 (PIP5Kalpha) 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 PIP5Kalpha 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 PIP5Kalpha 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 PIP5Kalpha knockdown strongly reduced ganglioside-induced transcription of proinflammatory cytokines IL-1beta and TNFalpha. PIP5Kalpha knockdown also suppressed ganglioside-induced phosphorylation and nuclear translocation of NF-kappaB and the degradation of IkappaB-alpha, indicating that PIP5Kalpha knockdown interfered with the ganglioside-activated NF-kappaB signaling. Together, these results suggest that PIP5Kalpha is a novel inflammatory mediator that undergoes upregulation and contributes to immune responses by facilitating NF-kappaB activation in ganglioside-stimulated astrocytes.
