标题:Luteolin-7-O-glucoside Suppresses Leukotriene C4 Production and Degranulation by Inhibiting the Phosphorylation of Mitogen Activated Protein Kinases and Phospholipase Cγ1 in Activated Mouse Bone Marrow-Derived Mast Cells
摘要:In this study, luteolin-7- O -glucoside (L7G), an herbal medicine isolated from Ailanthus altissima , inhibited 5-lipoxygenase (5-LOX)-dependent leukotriene C4 (LTC4) production in bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner with an IC50 of 3.0 μ M . To determine the action mechanism of L7G, we performed immunoblotting for cytosolic phospholipase A2 (cPLA2) and mitogen-activated protein kinases (MAPKs) following c-kit ligand (KL)-induced activation of BMMCs with or without L7G. Inhibition of LTC4 production by L7G was accompanied by a decrease in cPLA2 phosphorylation, which occurred via the extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 and c-Jun N-terminal kinase (JNK) pathways. In addition, L7G also attenuated mast cell degranulation in a dose-dependent manner (IC50, 22.8 μ M ) through inhibition of phospholipase Cγ1 (PLCγ1) phosphorylation. Our results suggest that the anti-asthmatic activity of L7G may be mediated in part via the inhibition of LTC4 generation and mast cell degranulation.
关键词:luteolin-7-O-glucoside;bone marrow-derived mast cell;degranulation;phospholipase Cγ1;leukotriene C4;mitogen activated protein kinase