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KMID : 0606920150230050421
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Biomolecules & Therapeutics
2015 Volume.23 No. 5 p.421 ~ p.427
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Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells
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Jeong Kyu-Tae
Lee Eu-Jin
Park Na-Young
Kim Sun-Gun
Park Hyo-Hyun
Lee Jie-An
Lee Youn-Ju
Lee Eun-Kyung
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Abstract
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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.
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KEYWORD
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Leukotriene C4, Prostaglandin D2, Cytosolic phospholipase A2, Mitogen-activated protein kinases, Phospholipase Cγ1
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