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

姜黄素对小鼠Th2致敏和肥大细胞功能的抑制作用

• 批准号: 8767779
• 负责人: Clinton B Mathias
• 金额: $ 34.85万
• 依托单位: WESTERN NEW ENGLAND UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8767779
• 关键词: Acute; Affect; Allergens; Allergic; Allergic Disease; Anaphylaxis; Anti-Allergic Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antibody Formation; Antigen-Presenting Cells; Aspergillus; Asthma; Automobile Driving; Blood; Bone Marrow; Cell Count; Cell physiology; Cells; Characteristics; Clinical Trials; Conjunctivitis; Crohn' s disease; Curcumin; Data; Development; Diarrhea; Disease; Disease Outcome; Edema; Eosinophilia; Evaluation; Exhibits; Food Hypersensitivity; Functional disorder; Goals; Guinea; Homeostasis; IgE; IgG1; Immune system; Individual; Infiltration; Inflammatory; Ingestion; Interleukin-10; Intestines; Investigation; Latex; Latex allergy; Mediating; Mediator of activation protein; Mission; Modeling; Mus; NF-kappa B; National Institute of Allergy and Infectious Disease; Ovalbumin; Pathology; Patients; Permeability; Phase; Phenotype; Play; Prevalence; Production; Property; Recombinants; Regulation; Role; Spices; Symptoms; T-Lymphocyte; Testing; Th2 Cells; Therapeutic; Therapeutic Agents; Tumeric; United States; Vomiting; airway hyperresponsiveness; allergic response; base; cytokine; eosinophil; food allergen; food antigen; gastrointestinal; in vivo; macrophage; mast cell; mouse model; novel; prevent; protective effect; public health relevance; response; undergraduate student

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.

描述（由申请人提供）：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%。过敏个体产生的过敏原特异性 IgE 水平升高，疾病的发展是由偏向 Th2 表型的 T 细胞（Th2 细胞）以及肥大细胞驱动的，导致呕吐、腹泻和胃肠道反应 功能障碍。在这项提案中，我们想确定频繁摄入姜黄素（咖喱香料姜黄的活性成分）是否可以抑制食物过敏小鼠模型的过敏反应。姜黄素具有众所周知的抗炎和抗过敏特性，并已被证明可以减少哮喘、乳胶过敏和结膜炎模型中的过敏反应。此外，它作为治疗剂的作用已经成为许多临床试验的主题。我们将重点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性反应的机制，我们认为这与 NIAID 的使命相关。我们假设姜黄素抑制 Th2 细胞对食物抗原的全身敏感性，并抑制肠道中肥大细胞的活化和功能，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 NF-κB 激活来介导的。这些假设将通过研究姜黄素在卵清蛋白 (OVA) 诱导的肠道过敏反应小鼠模型中的作用来检验。该模型中的过敏小鼠表现出严重腹泻、肠水肿等与食物过敏患者一致的特征。 Th2 细胞和肥大细胞及其介质在驱动过敏反应中发挥作用。将研究以下具体目标： 1. 确定 OVA 致敏前接触姜黄素是否会抑制过敏原特异性 Th2 反应的发展。 2. 评估姜黄素的抑制作用是否具有肥大细胞依赖性；将在 OVA 攻击期间或之后对暴露于姜黄素的小鼠进行疾病结果评估。 3.确定姜黄素的保护作用是否依赖于IL-10的抑制。

项目成果

Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy.

• DOI: 10.1371/journal.pone.0132467
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kinney SR;Carlson L;Ser-Dolansky J;Thompson C;Shah S;Gambrah A;Xing W;Schneider SS;Mathias CB
• 通讯作者: Mathias CB

IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.

IL-10能增强IgE介导的肥大细胞反应，对IL-10缺陷小鼠实验性食物过敏的发生至关重要

• DOI: 10.4049/jimmunol.1600066
• 发表时间: 2016-06-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Polukort SH;Rovatti J;Carlson L;Thompson C;Ser-Dolansky J;Kinney SR;Schneider SS;Mathias CB
• 通讯作者: Mathias CB

Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy.

• DOI: 10.3389/fimmu.2020.606837
• 发表时间: 2020
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Krajewski D;Polukort SH;Gelzinis J;Rovatti J;Kaczenski E;Galinski C;Pantos M;Shah NN;Schneider SS;Kennedy DR;Mathias CB
• 通讯作者: Mathias CB

Epigenetic Regulation via Altered Histone Acetylation Results in Suppression of Mast Cell Function and Mast Cell-Mediated Food Allergic Responses.

• DOI: 10.3389/fimmu.2018.02414
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Krajewski D;Kaczenski E;Rovatti J;Polukort S;Thompson C;Dollard C;Ser-Dolansky J;Schneider SS;Kinney SRM;Mathias CB
• 通讯作者: Mathias CB