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Calcium (Ca2+) is a ubiquitous second messenger regulating a myriad of cellular processes including proliferation, metabolism, and cell death. Increased cytosolic Ca2+ activates apoptosis and is cy...

IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. Herein we demonstrate a novel role for IL-10 in the development of IgE-mediated food allergy. Oral ovalbumin challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis including diarrhea, mast cell activation, and Th2 cytokine production was significantly attenuated in IL-10−/− mice compared to WT controls. Furthermore, IL-10 directly promoted the activation of mast cells. Administration of IgE and antigen induced the development of passive anaphylaxis in WT mice, which was attenuated in IL-10−/− animals. However, treatment of IL-10−/− mice with recombinant IL-10 prior to IgE administration restored the development of passive anaphylaxis in these animals. Finally, adoptive transfer of WT mast cells restored allergic symptoms in IL-10−/− mice. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell activation, suggesting that in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms.

Mast cells play critical roles in the establishment of allergic responses to food antigens. We have previously shown that frequent ingestion of the curry spice curcumin, inhibits mast cell expansion and suppresses intestinal anaphylaxis in a murine model of ovalbumin (OVA)-induced food allergy. Here, we demonstrate that the protective effects of curcumin are conferred during the mast cell-dependent, OVA-challenge phase of the model and are mediated by inhibition of NF-κB activation. Exposure to curcumin during OVA-challenge, but not OVA-sensitization, results in inhibition of allergic diarrhea, intestinal mastocytosis and Th2 cytokine production. This suggests that while curcumin has limited inhibitory effects on Th2 sensitization, it has direct suppressive effects on mast cell homeostasis and function. Suppression of mast cell activation was also associated with inhibition of NF-κB in OVA-gavaged, curcumin-treated animals suggesting that the inhibitory effects of curcumin may be mediated in an NF-κB-dependent manner. In summary, our data demonstrate that curcumin inhibits allergic responses to food antigens by blocking NF-κB activation and suppression of mast cell-dependent responses.

IgE antibodies and mast cells play critical roles in the establishment of allergic responses. Curcumin, the active ingredient of the naturally occurring curry spice turmeric, has anti-allergic properties, both in vitro and in vivo, and thus may have the capacity to modulate mucosal mast cell activation and function during allergic responses. Here, we show that curcumin inhibits the proliferation, survival and function of bone-marrow derived mast cells (BMMCs). BMMCs were grown in the presence of IL-3+SCF or monomeric IgE for 6 days. Co-culture with curcumin completely inhibited the proliferation and long-term survival of BMMCs, suggesting that curcumin has suppressive effects on mast cell expansion. Similarly, curcumin also suppressed the proliferation of peritoneal mast cells. Flow cytometric analysis of the BMMCs demonstrated that curcumin-treated BMMCs were undergoing apoptosis, as indicated by expression of Annexin V and propidium iodide. Intracellular cytokine staining further suggested that these BMMCs produced lower levels of TNF-α. Finally, curcumin-treated BMMCs, activated in the presence of antigen, exhibited reduced β-hexosaminidase activity in comparison with vehicle-treated controls. Our data demonstrate that dietary components such as curcumin can regulate the expansion, activation and function of mast cells, and thus may affect the outcome of mast-cell-dependent allergic responses in vivo.