Mast cells (MCs) are an important treatment target for high-affinity
IgE Fc receptor (FcεRI)-mediated allergic diseases. The plant-derived molecule
4-methylumbelliferone (4-MU) has beneficial effects in animal models of
inflammation and autoimmunity diseases. The aim of this study was to examine 4-MU effects on MC activation and probe the underlying molecular mechanism(s). We sensitized rat basophilic
leukemia cells (RBLs) and mouse bone marrow-derived mast cells (BMMCs) with anti-dinitrophenol (DNP)
immunoglobulin (Ig)E
antibodies, stimulated them with exposure to DNP-
human serum albumin (HSA), and then treated stimulated cells with 4-MU. Signaling-
protein expression was determined by immunoblotting. In vivo allergic responses were examined in
IgE-mediated passive cutaneous anaphylaxis (PCA) and
ovalbumin (OVA)-induced active systemic
anaphylaxis (ASA) mouse models. 4-MU inhibited β-
hexosaminidase activity and histamine release dose-dependently in FcεRI-activated RBLs and BMMCs. Additionally, 4-MU reduced cytomorphological elongation and
F-actin reorganization while down-regulating
IgE/Ag-induced phosphorylation of SYK, NF-κB p65, ERK1/2, p38, and JNK. Moreover, 4-MU attenuated the PCA
allergic reaction (i.e., less ear thickening and
dye extravasation). Similarly, we found that 4-MU decreased body temperature, serum
histamine, and
IL4 secretion in OVA-challenged ASA model mice. In conclusion, 4-MU had a suppressing effect on MC activation both in vitro and in vivo and thus may represent a new strategy for treating
IgE-mediated allergic conditions.