Contribution of TLR2 to the Initiation of Ganglioside-triggered Inflammatory Signaling

  • Yoon, Hee Jung (Immune and Cell therapy Branch, National Cancer Center) ;
  • Jeon, Sae Bom (Immune and Cell therapy Branch, National Cancer Center) ;
  • Suk, Kyoungho (Department of Pharmacology, Kyungbook National University School of Medicine) ;
  • Choi, Dong-Kug (Department of Biotechnology, Konkuk University) ;
  • Hong, Young-Joon (Department of Laboratory Medicine, Korea Cancer Center Hospital) ;
  • Park, Eun Jung (Immune and Cell therapy Branch, National Cancer Center)
  • Received : 2007.07.16
  • Accepted : 2007.08.03
  • Published : 2008.02.29

Abstract

Gangliosides, sialic acid-containing glycosphingolipids, are implicated in many neuronal diseases, but the precise molecular mechanisms underlying their pathological activities are poorly understood. Here we report that TLR2 participates in the initiation of ganglioside-triggered inflammatory signaling responses. Using FACS analysis and immunofluorescence microscopy, we found that gangliosides rapidly enhanced the cell surface expression of TLR2 in microglia, while reducing that of TLR4. The ganglioside-dependent increase of TLR2 expression was also observed at the messenger and protein levels. We also showed that gangliosides stimulate the interaction of TLR2 with Myd88, an adaptor for TLRs, and obtained evidence that lipid raft formation is closely associated with the ganglioside-induced activation of TLR2 and subsequent inflammatory signaling. These results collectively suggest that TLR2 contributes to the ability of gangliosides to cause inflammatory conditions in the brain.

Keywords

Adaptor;Astrocytes;Brain;Endogenous Ligand;Gangliosides;Inflammation;Microglia;Myd88;TLR2

Acknowledgement

Supported by : Korea Research Foundation, Korea Science and Engineering Foundation

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