The Effect of Bromelain on CD4+ T Cell Function in Asthma

菠萝蛋白酶对哮喘 CD4 T 细胞功能的影响

基本信息

批准号：
7471622
负责人：
Eric Richard Secor
金额：
$ 13.46万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7471622
关键词：
5-(6)-carboxyfluorescein diacetate succinimidyl ester Acute Address Annexins Anti-Inflammatory Agents Anti-inflammatory Antibodies Antigen Presentation Antigen-Presenting Cells Apoptosis Area Asthma Award B-Lymphocytes Biological Assay Biological Factors Botanicals Bronchoalveolar Lavage CD11 Antigens CD19 gene CD22 gene CD28 gene CD4 Positive T Lymphocytes CD44 gene CD80 gene Cell Surface Receptors Cell physiology Cell surface Cells Chronic Condition Connecticut Consultations Culture Media D Cells Data Dendritic Cells Development Disease Enzyme-Linked Immunosorbent Assay Fellowship Flow Cytometry General Population Goals Health Hilar Histology Hypersensitivity IL2 Signaling Pathway IL2RA gene IL2RB gene IL2RG gene IL6 Signaling Pathway IgE Immune system Immunoglobulin G Immunohistochemistry Immunology In Situ Nick-End Labeling In Vitro Inguinal lymph node group Interleukin 2 Receptor Interleukin 6 Receptor Interleukin-2 Janus kinase Licensing MS4A1 gene Mentorship Messenger RNA Mission Mitogen-Activated Protein Kinases Modeling Names National Center for Complementary and Alternative Medicine Ovalbumin PTPRC gene Pathway interactions Physicians Pineapple (Fruit)Postdoctoral Fellow Rate Research Research Personnel Research Training Reverse Transcriptase Polymerase Chain Reaction SELL gene Serum Signal Transduction Spleen Staging Staining method Stains Structure of parenchyma of lung T-Cell Activation T-Lymphocyte TNFRSF5 gene Therapeutic Training Translational Research Treatment Protocols Universities allergic airway disease career cytokine eosinophil in vivo lymph nodes mouse model programs research study stem

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a development award for Dr. Secor, a Naturopathic Physician and Licensed Acupuncturist, to successfully achieve his long term career goals of becoming an independent investigator focused on the immunomodulatory effects of natural products through translational research. This proposal combines advanced academics, research training, outstanding mentorship and consultation to promote professional career development. Dr. Secor has successfully completed a NIH/NCCAM F32 Post Doctoral Fellowship at the University of Connecticut Health Center in the Department of Immunology. His research has demonstrated that Bromelain (Br), a pineapple extract, exerted anti-inflammatory and immunomodulatory effects in an ovalbumin (OVA)-induced mouse model of allergic airway disease (AAD) via reduced CD4+ T cells, eosinophils, and Th2 cytokines. We have observed that Br treatment reduces CD25, a key activation marker on CD4+ T cells as well as alters MHC-II and CD86 levels on antigen presenting cells (APCs), such as Dendritic Cells (DCs) and B cells. We hypothesize that the therapeutic benefits of Br in this OVA-induced model occur via immunomodulatory effects on CD4+ T cells specifically by: 1) Direct inhibition of CD4+ T cell activation via IL-2 signaling, 2) Direct inhibition of antigen presenting cells (DCs and B cells). Specific Aim 1 will determine the in vivo effects of Br treatment on CD4+ T cells and APCs in local compartments (BAL, lung tissue, hilar lymph nodes) and systemic compartments (inguinal lymph nodes, spleen) at each of the 4 stages of the OVA model: Sensitization, AAD, Continuous LIT and Discontinuous AAD. Specific Aim 2 will determine the specific mechanism(s) of action of Br by in vitro treatment of CD4+ T cells, DCs and B cells isolated from local and systemic compartments during the 4 stages of the OVA model. Botanicals with unknown mechanisms of action are widely used by the general public in the treatment and management of acute and chronic conditions such as allergy and asthma. The effect of botanicals and their extracts on the immune system is an exciting new area of research. These studies will help elucidate the anti-inflammatory mechanism(s) of action of Br and provide rigorous advanced training to a CAM clinician, all of which are directly relevant to the mission of NCCAM.

描述（由申请人提供）：该提案描述了为自然疗法医师和执业针灸师 Secor 博士提供的发展奖，以成功实现他的长期职业目标，成为一名专注于通过转化研究天然产物的免疫调节作用的独立研究者。该提案将先进的学术、研究培训、杰出的指导和咨询结合起来，以促进职业生涯发展。 Secor 博士已在康涅狄格大学健康中心免疫学系成功完成 NIH/NCCAM F32 博士后奖学金。他的研究表明，菠萝提取物菠萝蛋白酶 (Br) 通过减少 CD4+ T 细胞、嗜酸性粒细胞和 Th2 细胞因子，在卵清蛋白 (OVA) 诱导的过敏性气道疾病 (AAD) 小鼠模型中发挥抗炎和免疫调节作用。我们观察到 Br 治疗会降低 CD25（CD4+ T 细胞的关键激活标记物），并改变抗原呈递细胞 (APC)（例如树突状细胞 (DC) 和 B 细胞）上的 MHC-II 和 CD86 水平。我们假设 Br 在 OVA 诱导模型中的治疗效果是通过对 CD4+ T 细胞的免疫调节作用实现的，特别是：1) 通过 IL-2 信号传导直接抑制 CD4+ T 细胞活化，2) 直接抑制抗原呈递细胞 (DC)和 B 细胞）。具体目标 1 将确定 Br 治疗对 OVA 4 个阶段中局部区室（BAL、肺组织、肺门淋巴结）和全身区室（腹股沟淋巴结、脾脏）中 CD4+ T 细胞和 APC 的体内影响模型：敏化、AAD、连续 LIT 和不连续 AAD。具体目标 2 将通过在 OVA 模型的 4 个阶段中对从局部和全身区室分离的 CD4+ T 细胞、DC 和 B 细胞进行体外处理，确定 Br 的具体作用机制。作用机制未知的植物药被公众广泛用于治疗和管理过敏和哮喘等急慢性疾病。植物及其提取物对免疫系统的影响是一个令人兴奋的新研究领域。这些研究将有助于阐明 Br 的抗炎作用机制，并为 CAM 临床医生提供严格的高级培训，所有这些都与 NCCAM 的使命直接相关。