Selinidin suppresses IgE-mediated mast cell activation by inhibiting multiple steps of Fc epsilonRI signaling.
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 (Fc epsilonRI) 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 selinidin attenuates the release of beta-hexosaminidase, synthesis of leukotriene C4, and production of tumor necrosis factor-alpha without affecting IgE-Fc epsilonRI binding. Furthermore, biochemical analyses of the Fc epsilonRI-mediated signaling pathway demonstrated that selinidin decreases phosphorylation of phospholipase C-gamma1, p38 mitogen-activated protein kinase, and IkappaB-alpha upon FcepsilonRI stimulation. These results suggest that this compound suppresses IgE-mediated mast cell activation by inhibiting multiple steps of FcepsilonRI-dependent signaling pathways and would be beneficial for the prevention of allergic inflammation.
Kishiro
Sachiko
S
Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Science, 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo 173-8610, Japan.
Nunomura
Satoshi
S
Nagai
Hisashi
H
Akihisa
Toshihiro
T
Ra
Chisei
C
D029969:Angelica / Q000737:chemistry; D000818:Animals; D018926:Anti-Allergic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology / Q000502:physiology*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000302:isolation & purification; D018547:Plant Stems / Q000737:chemistry; D017455:Receptors, IgE / Q000037:antagonists & inhibitors*
D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D003374:Coumarins; D010936:Plant Extracts; D017455:Receptors, IgE; C528104:selinidin; D007073:Immunoglobulin E