Spiraeoside inhibits mast cells activation and IgE-mediated allergic responses by suppressing phospholipase C-γ-mediated signaling

Abstract

Mast cells are responsible for IgE-mediated allergic responses through the secretion of various inflammatory cytokines and mediators. Therefore, the pharmacological regulation of mast cell activation is an important goal in the development of novel anti-allergic drugs. In this study, we found that spiraeoside (SP) inhibits mast cell activation and allergic responses in vivo. SP dose-dependently inhibited the degranulation induced by IgE-antigen (Ag) stimulation in RBL-2H3 mast cells without cytotoxic effects. At the molecular level, SP reduced the Ag-induced phosphorylation and subsequent activation of phospholipase C-γ2 (PLC-γ2). Moreover, SP inhibited the phosphorylation of spleen tyrosine kinase (Syk), linker for activation of T cells (LAT), and downstream MAPKs, such as ERK1/2, p38, and JNK, eventually attenuating expression of TNF-α and IL-4. Finally, we found that SP significantly inhibited IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Taken together, our results strongly suggest that SP suppresses IgE-mediated mast cell activation and allergic responses by inhibiting Lyn-induced PLC-γ2/MAPK signaling in mast cells.

Polydatin inhibits mast cell-mediated allergic inflammation by targeting PI3K/Akt, MAPK, NF-κB and Nrf2/HO-1 pathways

“…PLCγ hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to diacylglycerol (DAG) and IP3. DAG is reported to activate PKC, which stimulates IKK complex, and IP3 ultimately triggers extracellular calcium influx 45 . IKK stimulation and increased intracellular calcium level provoke the secretion and expression of allergic mediators.…”

Vitamin D contributes to mast cell stabilization

“…Both mediators are presynthesized and deposited in mast cells and can be released immediately upon activation. The IgE‐induced mast cell activation, to inhibit Syk and LAT, can suppress the release of TNF‐α and inhibit allergic response . Our data show that VDR not only interacts with the β chain of FcεRI in mast cells, but also binds to the promoter of TNF‐α and represses its transcription and expression.…”

Mast Cells in Allergy: The Potential Molecular Targets in the Upstream Signalling Pathways

“…Apart from that, many potential MC stabilizers from natural sources have been extensively identified over the years. Among which, Streptochlorin and Spiraeoside have been shown to attenuate IgE-mediated MC degranulation using rat basophilic leukemia (RBL) 2H3 cell line and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice (Kim et al, 2015;Lee et al, 2013). Specifically, these two compounds attenuate the phosphorylation of Syk in RBL-2H3 cells which eventually inhibit the downstream signalling molecules such as Lyn, Fyn, and MAPK proteins (Kim et al, 2015;Lee et al, 2013).…”