title: Contribution of TLR2 to the initiation of ganglioside-triggered inflammatory signaling.
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.
authors.affiliation: Immune and Cell therapy Branch, National Cancer Center, Koyang 410-769, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Sae Bom
authors.initials: SB
authors.lastname: Jeon
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Hong
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Park
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000378:metabolism
chemical_list: D005732:Gangliosides; D053594:Myeloid Differentiation Factor 88; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin