Abstract

IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.

Highlights

  • Food allergy is an emerging public health problem worldwide [1,2,3,4]

  • We chose to use a well-established model of intestinal anaphylaxis for our studies on the effects of curcumin during allergic responses to food antigens [10, 34, 38]

  • Based on studies that curcumin inhibits T cell and mast cell functions, we hypothesized that oral ingestion of curcumin during allergic sensitization and challenge would inhibit the development of intestinal anaphylaxis to food antigens

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Summary

Introduction

Food allergy is an emerging public health problem worldwide [1,2,3,4]. Severe anaphylactic reactions to food products underscore the need for research to better understand the mechanisms by which food antigens stimulate the gastrointestinal tract and impair tolerance to ingested food particles. There is a need to develop therapeutic agents that either prevent sensitization to food antigens or suppress the allergic response after initiation. IgE and mast cells play a crucial role in the development of allergic responses to food antigens [2, 5,6,7]. Patients with food allergies produce elevated levels of allergen-specific IgE and exhibit both eosinophilic and mast cell inflammation in the gastrointestinal tract [7, 8]. The allergic phenotype is driven by Th2 cells, producing high levels of the cytokines IL-4, IL-5, IL-9, and IL-13 in the intestinal mucosa [14, 15]

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