3-O-(2,3-dimethylbutanoyl)-13-O-decanoylingenol from Euphorbia kansui suppresses IgE-mediated mast cell activation.
Aggregation of the high affinity receptor for IgE (FcepsilonRI) on mast cells by antigen and IgE complex induces release of chemical mediators, leading to acute allergic inflammation. We recently found that 3-O-(2,3-dimethylbutanoyl)-13-O-decanoylingenol (DBDI), purified from the Euphorbia kansui L., inhibits degranulation in rat basophilic leukemia 2H3 cells upon aggregation of the FcepsilonRI. In the present study, we demonstrated that the DBDI significantly inhibits release of beta-hexosaminidase, synthesis of eicosanoids, and mobilization of intracellular Ca(2+) in the bone marrow-derived mouse mast cells stimulated with IgE and antigen. Furthermore, we revealed that phosphorylation of Syk, phospholipase C-gamma(2), and extracellular signal-related kinase 1/2 is significantly suppressed in the DBDI-treated mast cells. These findings suggest that the DBDI may have a therapeutic potential for allergic diseases by inhibiting intracellular signaling pathways for activation and chemical mediator release in mast cells.
Nunomura
Satoshi
S
Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Sciences.
Kitanaka
Susumu
S
Ra
Chisei
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry*; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018517:Plant Roots / Q000737:chemistry; D017455:Receptors, IgE / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
C508533:3-O-(2,3-dimethylbutanoyl)-13-O-decanoylingenol; D004224:Diterpenes; D015777:Eicosanoids; D017455:Receptors, IgE; D007073:Immunoglobulin E; D001619:beta-N-Acetylhexosaminidases; D002118:Calcium