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）：该提案描述了自然疗法医师和有执照的针灸师Secor博士的发展奖，以成功地实现了他的长期职业生涯目标，即通过翻译研究成为针对天然产品的免疫调节作用的独立研究者。该提案结合了高级学者，研究培训，杰出的指导和咨询，以促进职业职业发展。 Secor博士在免疫学系的康涅狄格大学健康中心成功完成了NIH/NCCAM F32博士后奖学金。他的研究表明，Bromelain（BR）是一种菠萝提取物，通过减少的CD4+ T细胞，嗜酸性粒细胞和Th2细胞因子的CD4+ T细胞，通过减少的CD4+ T细胞，卵形蛋白（OVA）诱导的小鼠诱导的小鼠模型施加了抗炎和免疫调节作用。我们已经观察到BR处理可减少CD25，这是CD4+ T细胞上的键激活标记，以及在抗原呈递细胞（APC）上改变MHC-II和CD86水平，例如树突状细胞（DCS）和B细胞。我们假设在该OVA诱导的模型中，BR的治疗益处是通过对CD4+ T细胞的免疫调节作用而发生的，特别是：1）直接抑制通过IL-2信号传导CD4+ T细胞激活，2）直接抑制抗原呈现的细胞（DC和B细胞）。具体目标1将确定BR治疗对局部区室（BAL，肺组织，肺淋巴结）和全身室（腹膜淋巴结，脾脏）在OVA模型的每个四个阶段中的体内效应（BAL，肺组织，肺淋巴结）（腹股沟淋巴结，脾脏，脾脏）。特定目标2将通过在OVA模型的4个阶段中从本地和全身室分离的CD4+ T细胞，DC和B细胞的体外处理来确定BR作用的特定机制。公众在急性和慢性病（例如过敏和哮喘）的治疗和管理中广泛使用了具有未知作用机制的植物学。植物及其提取物对免疫系统的影响是令人兴奋的新研究领域。这些研究将有助于阐明BR作用的抗炎机制，并为CAM临床医生提供严格的先进培训，所有这些培训与NCCAM的任务直接相关。