Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells.
Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cγ1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-κB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.
Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210.
Kyu-Tae
KT
Jeong
Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210.
Eujin
E
Lee
Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210.
Na-Young
NY
Park
Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210.
Sun-Gun
SG
Kim
Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210.
Hyo-Hyun
HH
Park
R&D Center, Morechem Co., Ltd, Yongin 446-908.
Jiean
J
Lee
School of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
Youn Ju
YJ
Lee
Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210.
Eunkyung
E
Lee
Cytosolic phospholipase A2; Leukotriene C4; Mitogen-activated protein kinases; Phospholipase Cγ1; Prostaglandin D2