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

描述(由申请人提供)：本提案描述了为自然疗法医生和有执照的针灸医生Secor博士设立的发展奖，以成功实现他的长期职业目标，即通过翻译研究成为一名专注于天然产品免疫调节效果的独立调查员。这一建议结合了先进的学术、研究培训、杰出的导师和咨询，以促进职业生涯发展。塞科尔博士在康涅狄格大学健康中心免疫学系成功完成了NIH/NCCAM F32博士后奖学金。他的研究表明，菠萝提取物菠萝酶(BR)通过减少CD4+T细胞、嗜酸性粒细胞和Th2细胞因子，在卵蛋白(OVA)诱导的过敏性呼吸道疾病(AAD)小鼠模型中发挥抗炎和免疫调节作用。我们观察到，BR治疗降低了CD4+T细胞上的关键激活标志CD25，并改变了抗原提呈细胞(APC)上的MHC-II和CD86水平，如树突状细胞(DC)和B细胞。我们推测BR在这个OVA诱导的模型中的治疗作用是通过免疫调节作用来实现的：1)通过IL-2信号直接抑制CD4+T细胞的激活；2)直接抑制抗原提呈细胞(DC和B细胞)。具体目标1将确定BR治疗对OVA模型4个阶段(致敏、AAD、持续LIT和不连续AAD)局部间隔(BAL、肺组织、肺门淋巴结)和全身间隔(腹股沟淋巴结、脾)中的CD4+T细胞和APC的体内影响。特异靶2将通过体外处理卵巢癌模型4个阶段的局部和全身隔室分离的CD_4~+T细胞、DC和B细胞来确定BR的特殊作用机制(S)。作用机制未知的植物药被公众广泛用于治疗和管理急性和慢性疾病，如过敏和哮喘。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的抗炎机制(S)，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。

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.