Selinidin Suppresses IgE-Mediated Mast Cell Activation by Inhibiting Multiple Steps of FcεRI Signaling

Sachiko Kishiro, Satoshi Nunomura, Hisashi Nagai, Toshihiro Akihisa, Chisei Ra
2008 Biological and Pharmaceutical Bulletin  
IgE -mediated mast cell activation is critical for development of allergic inflammation. We have recently found that selinidin, one of the coumarin derivatives isolated from Angelica keiskei, attenuates mast cell degranulation following engagement of the high-affinity receptor for IgE (Fce e RI) with IgE and antigen. In the present study, we investigated the effects of selinidin on intracellular signaling and mast cell activation employing bone marrow-derived mast cells. Here, we report that
more » ... inidin attenuates the release of b b-hexosaminidase, synthesis of leukotriene C 4 , and production of tumor necrosis factor-a a without affecting IgE-Fce e RI binding. Furthermore, biochemical analyses of the Fce e RI-mediated signaling pathway demonstrated that selinidin decreases phosphorylation of phospholipase C-g g1, p38 mitogen-activated protein kinase, and Ik kB-a a upon Fce eRI stimulation. These results suggest that this compound suppresses IgE-mediated mast cell activation by inhibiting multiple steps of Fce e RI-dependent signaling pathways and would be beneficial for the prevention of allergic inflammation.
doi:10.1248/bpb.31.442 pmid:18310907 fatcat:6sbzmfiayfdytboqrwyibfjkgy