Biomolecules & Therapeutics  2014;22(3):193-199

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway.

Yue LU 1 ; Xian LI ; Young Na PARK ; Okyun KWON ; Donggen PIAO ; Young Chae CHANG ; Cheorl Ho KIM ; Eunkyung LEE ; Jong Keun SON ; Hyeun Wook CHANG

Affiliations

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Keywords

Britanin; Mast cells; Eicosanoid; Degranulation; Syk kinase; Mitogen-activated protein kinase; Allergic inflammation

Country

Republic of Korea

Language

English

Abstract

The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of PGD2 and LTC4 in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase Cgamma1 (PLCgamma1)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase and p38), and the nuclear factor-kappaB (NF-kappaB) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.