Passive Anaphylaxis Mouse Model Research Articles

Inhibitory effect of the Larix sibirica and its various flavonoids on the IgE-stimulated mast cell activation and anaphylaxis

Larix sibirica (Siberian larch) is a deciduous tree native to Russia, Mongolia, and China and has been reported to possess anti-viral, anti-oxidant, and neuroprotective properties. In this study, we assessed the anti-allergic effects of an L. sibirica extract (LSE) and its various flavonoids using an IgE-sensitized mast cell-like cell line, rat basophilic leukaemia (RBL)-2H3, and a passive anaphylaxis mouse model. In IgE-sensitized RBL-2H3 cells, LSE and several flavonoids reduced release and production of β-hexosaminidase, histamine, and inflammatory mediators (prostaglandin D2, leukotriene C4, interleukin-4, and tumour necrosis factor-α), reduced expression of cyclooxygenase-2 and 5-lipoxygenase, and suppressed activation of nuclear factor-κB. LSE and several flavonoids reduced phosphorylation of downstream signalling molecules, such as Syk, protein kinase Cµ, phospholipase Cγ, and mitogen-activated protein kinases. Oral administration of LSE inhibited mast cell-dependent passive cutaneous anaphylactic reactions. These results suggest that LSE is a beneficial candidate for the prevention and treatment of allergic disorders.

NecroX-5 suppresses IgE/Ag-stimulated anaphylaxis and mast cell activation by regulating the SHP-1-Syk signaling module.

IgE/Ag-stimulated mast cells release various pro-allergic inflammatory mediators, including histamine, eicosanoids, and pro-inflammatory cytokines. NecroX-5, a cell permeable necrosis inhibitor, showed cytoprotective effects in both in vitro and in vivo models. However, the anti-allergic effect of NecroX-5 has not yet been investigated. The aims of this study were to evaluate the anti-allergic activity of NecroX-5 in vivo and to investigate the underlying mechanism in vitro. The anti-allergic activity of NecroX-5 was evaluated in vitro using bone marrow-derived mast cells (BMMCs) and IgE receptor-bearing RBL-2H3 or KU812 cells and in vivo using a mouse model of passive anaphylaxis. The levels of histamine, eicosanoids (PGD2 and LTC4 ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using enzyme immunoassay kits. The mechanism underlying the action of NecroX-5 was investigated using immunoblotting, immunoprecipitation, and gene knockdown techniques. NecroX-5 markedly inhibited mast cell degranulation and the synthesis of eicosanoids, TNF-α, and IL-6 by suppressing the activation of Syk, LAT, phospholipase Cγ1, MAP kinases, the Akt/NF-κB pathway, and intracellular Ca(2+) mobilization via the activation of phosphatase SHP-1. Oral administration of NecroX-5 effectively suppressed mast cell-dependent passive cutaneous and systemic anaphylactic reactions in a dose-dependent manner. NecroX-5 might be a potential candidate for the development of a novel anti-allergic agent that suppresses IgE-dependent mast cells signaling.