Biol. Pharm. Bull. 29(2) 286—290 (2006)

(FceRI) on the cell surface which plays a pivotal role in the development of allergic inflammation. FceRI is mainly expressed on mast cells and basophils as a tetramer of one a , one b and g chain homodimers. Aggregation of the FceRI on mast cells by bound IgE and multivalent antigens induces rapid release of preformed intragranular mediators such as histamine and heparin, newly synthesis of arachidonic acid metabolites, such as prostaglandins (PGs) and leukotrienes (LTs). Activation of intracellular signaling is essential for these acute allergic reactions through FceRI. Namely, upon FceRI cross-linking, tyrosine phosphorylation of the b chain via activated-Lyn and subsequent phosphorylation of g chain and Syk by Lyn are immediately induced, which in turn leads to activation of phospholipase C (PLC)-g and linker for activation of T cells (LAT), intracellular Ca mobilization, activation of protein Kinase C (PKC) and mitogen activated protein (MAP) kinase family. A large number of studies revealed that suppression of Ca responses, PKC and MAP kinase family members has substantial inhibitory effects on release of histamine and generation of arachidonic acid metabolite in mast cells. The dried roots of Euphorbia kansui L. (E. kansui) are known as “Kan Sui” in Chinese medicine and have been used as herbal remedy for cancer or edema in the mainland of China. As for anti-tumor activity of E. kansui, it was reported that numerous diterpenes with an ingenol skeleton from the roots of the E. kansui suppress progression of cell cycle related to proliferation of cancer cells. Recently, we found that 3-O-(2,3-dimethylbutanoyl)-13-O-decanoylingenol (abbreviated thereafter as DBDI) from E. kansui has a potent inhibitory effect on release of b-hexosaminidase in rat basophilc leukemia 2H3 cells (RBL-2H3) following FceRI cross-linking (unpublished data). In this study, we investigated effects of DBDI on the activation of intracellular signaling pathways and the release of inflammatory chemical mediators in the bone marrow-derived mouse mast cells upon FceRI stimulation. Here, we report that DBDI-treated mast cells show a significant reduction of b-hexosaminidase release and eicosanoids synthesis when compared with non-treated cells. These suppressive actions of DBDI may be caused by inhibiting of intracellular signaling including Syk, PLC-g2, Ca responses and extracellular signal regulated kinase (ERK) 1/2. Our findings of the present study may provide useful information for antiallergic action of the DBDI against mast cell activation through FceRI.