BioMed Research International

Schmieg, John;Yang, Guangli;Franck, Richard W.;Tsuji, Moriya

doi: 10.1155/2010/283612pmid: 20069056

We have previously shown that the C-glycoside analog of <svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M2" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-galactosylceramide (<svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M3" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-GalCer), <svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M4" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-C-GalCer, displays a superior inhibitory activity against the liver stages of the rodent malaria parasite <i >Plasmodium yoelii</i> than its parental glycolipid, <svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M5" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-GalCer. In this study, we demonstrate that NK cells, as well as IL-12, are a key contributor for the superior activity displayed by <svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M6" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-C-GalCer. Surprisingly, the diminished production of Th2 cytokines, including IL-4, by <svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M7" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-C-GalCer has no affect on its superior therapeutic activity relative to <svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M8" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-GalCer. Finally, we show that the in vivo administration of <svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M9" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-C-GalCer induces prolonged maturation of dendritic cells (DCs), as well as an enhanced proliferative response of mouse invariant V<svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M10" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>14 (V<svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M11" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>14i) NKT cells, both of which may also contribute to some degree to the superior activity of <svg style="vertical-align:-0.1638pt;width:9.7749996px;" id="M12" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FC"/></g> </svg>-C-GalCer in vivo.