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

描述(申请人提供)：食物过敏在美国是一个日益严重的问题，估计患病率为3-6%。过敏性个体产生高水平的过敏原特异性IgE，疾病的发展是由偏向Th2表型(Th2细胞)的T细胞以及肥大细胞推动的，导致呕吐、腹泻和胃肠道 功能障碍。在这项建议中，我们想要确定频繁摄入姜黄素是否可以抑制食物过敏小鼠模型的过敏反应。姜黄素是咖喱香料的活性成分姜黄。姜黄素具有众所周知的抗炎和抗过敏特性，并已被证明可减少哮喘、乳胶过敏和结膜炎模型的过敏反应。此外，它作为治疗剂的作用已经成为一些临床试验的主题。我们将集中精力研究姜黄素在食物过敏过程中调节T细胞和肥大细胞依赖反应的机制，我们认为这与NIAID的使命有关。我们推测，姜黄素抑制Th2细胞对食物抗原的系统敏化，抑制肠道肥大细胞的激活和功能，从而抑制过敏性疾病的发展。我们还提出，摄入姜黄素将防止先前过敏的小鼠再次出现过敏症状。最后，我们认为这种保护作用是通过抑制IL-10和核因子-β的激活来实现的。这些假设将通过研究姜黄素在卵蛋白(OVA)诱导的肠道过敏反应小鼠模型中的作用来验证。在这个模型中，过敏小鼠表现出严重的腹泻、肠道水肿和其他与食物过敏患者表现出的特征一致的特征。Th2细胞和肥大细胞及其介体都在驱动过敏反应中发挥作用。将调查以下具体目标：1.确定卵清蛋白致敏前接触姜黄素是否抑制过敏原特异性Th2反应的发展。2.评估姜黄素的抑制作用是否依赖于肥大细胞；将在卵清蛋白攻击过程中或之后评估姜黄素对小鼠的疾病转归。3.确定姜黄素的保护作用是否依赖于对IL-10的抑制。

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.