Inhibitory effects of curcumin on Th2 sensitization and mast cell function in a m

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DESCRIPTION (provided by applicant): Food allergy is a growing problem in the United States with an estimated prevalence of 3-6%. Allergic individuals produce elevated levels of allergen-specific IgE, and development of the disease is driven by T cells biased towards a Th2 phenotype (Th2 cells), as well as mast cells, resulting in vomiting, diarrhea, and gastrointestinal dysfunction. In this proposal, we would like to determine whether frequent ingestion of curcumin, the active ingredient of the curry spice, turmeric, can inhibit allergic responses in a mouse model of food allergy. Curcumin has well-known anti-inflammatory and anti-allergic properties and has been shown to diminish allergic responses in models of asthma, latex allergy and conjunctivitis. In addition, its role as a therapeutic agent is already the subject of a number of clinical trials. We will focus our efforts on the mechanisms by which curcumin regulates T and mast cell-dependent responses during food allergy, which we believe is relevant to the mission of NIAID. We hypothesize that curcumin inhibits the systemic sensitization of Th2 cells to food antigens and suppresses mast cell activation and function in the gut, thereby inhibiting the development of allergic disease. We also propose that curcumin ingestion will prevent the re-occurrence of allergic symptoms in previously allergic mice. Finally, we suggest that this protective effect is mediated by inhibition of IL-10 and NF-?B activation. These hypotheses will be tested by studying the effects of curcumin in a well-established murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Allergic mice in this model exhibit severe diarrhea, intestinal edema and other characteristics consistent with those exhibited by patients with food allergy. Both Th2 cells and mast cells and their mediators play a role in driving the allergic response. The following specific aims will be investigated: 1. To determine whether curcumin exposure prior to sensitization with OVA inhibits the development of allergen-specific Th2 responses. 2. To assess whether the inhibitory effects of curcumin are mast cell-dependent; disease outcome will be evaluated in mice exposed to curcumin during or after OVA challenge. 3. To determine whether the protective effects of curcumin are dependent on inhibition of IL-10.