Contribution of TLR2 to the initiation of ganglioside-triggered inflammatory signaling.
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.
Yoon
Hee Jung
HJ
Immune and Cell therapy Branch, National Cancer Center, Koyang 410-769, Korea.
Jeon
Sae Bom
SB
Suk
Kyoungho
K
Choi
Dong-Kug
DK
Hong
Young-Joon
YJ
Park
Eun Jung
EJ
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
D005732:Gangliosides; D053594:Myeloid Differentiation Factor 88; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin