20(S)-Protopanaxatriol inhibits release of inflammatory mediators in immunoglobulin E-mediated mast cell activation.
BACKGROUND
Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction.METHODS
Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells.RESULTS
PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase A2 (PLA2), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, PLA2, and transcription factors (nuclear factor-κB and activator protein-1).CONCLUSION
PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the Ca(2+) influx, protein kinase C, and PLA2, which are propagated by Syk activation upon allergic stimulation of mast cells.
BACKGROUND
Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction.
METHODS
Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells.
RESULTS
PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase A2 (PLA2), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, PLA2, and transcription factors (nuclear factor-κB and activator protein-1).
CONCLUSION
PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the Ca(2+) influx, protein kinase C, and PLA2, which are propagated by Syk activation upon allergic stimulation of mast cells.