Effects of ART on Oral Epithelial Cell Biology

ART 对口腔上皮细胞生物学的影响

基本信息

批准号：
7478816
负责人：
CRAIG S MILLER
金额：
$ 18.11万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-02 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7478816
关键词：
Address Adverse effects Affect Anatomy Anti-Retroviral Agents Basic Science Biochemical Cause of Death Cell Differentiation process Cells Cellular biology Cessation of life Class Communicable Diseases Communication Disease Dyslipidemias Environment Enzyme-Linked Immunosorbent Assay Epithelial Epithelial Cells Epithelium Figs - dietary Functional disorder Goals HIV Health Homeostasis Human Human Papillomavirus Immune Immune response Immune system Individual Infection Inflammatory Knowledge Life Ligands Liquid substance Long-Term Effects Measures Medical Methodology Mitochondria Molecular Morbidity - disease rate Mouth Diseases Mucosal Immunity Mucous Membrane Natural Immunity Opportunistic Infections Oral Oral Medicine Oral Pathology Oral cavity Oral health Oral mucous membrane structure Pathology Pathway interactions Patients Pattern recognition receptor Peptide Hydrolases Pharmaceutical Preparations Population Positioning Attribute Process Production Receptor Signaling Recycling Research Research Design Risk Saliva Scientist Signal Pathway Signal Transduction Structure TLR2 gene TLR3 gene TLR4 gene Testing Tissues Toll-like receptors Ubiquitin Viral Virus Diseases antiretroviral therapy base chemokine cytokine fighting human TGFB1 protein immune function immunocytochemistry insight microbial mitochondrial dysfunction monolayer mortality multicatalytic endopeptidase complex oral cavity epithelium oral pathogen pathogen protein degradation response soft tissue

Address Adverse effects Affect Anatomy Anti-Retroviral Agents Basic Science Biochemical Cause of Death Cell Differentiation process Cells Cellular biology Cessation of life Class Communicable Diseases Communication Disease Dyslipidemias Environment Enzyme-Linked Immunosorbent Assay Epithelial Epithelial Cells Epithelium Figs - dietary Functional disorder Goals HIV Health Homeostasis Human Human Papillomavirus Immune Immune response Immune system Individual Infection Inflammatory Knowledge Life Ligands Liquid substance Long-Term Effects Measures Medical Methodology Mitochondria Molecular Morbidity - disease rate Mouth Diseases Mucosal Immunity Mucous Membrane Natural Immunity Opportunistic Infections Oral Oral Medicine Oral Pathology Oral cavity Oral health Oral mucous membrane structure Pathology Pathway interactions Patients Pattern recognition receptor Peptide Hydrolases Pharmaceutical Preparations Population Positioning Attribute Process Production Receptor Signaling Recycling Research Research Design Risk Saliva Scientist Signal Pathway Signal Transduction Structure TLR2 gene TLR3 gene TLR4 gene Testing Tissues Toll-like receptors Ubiquitin Viral Virus Diseases antiretroviral therapy base chemokine cytokine fighting human TGFB1 protein immune function immunocytochemistry insight microbial mitochondrial dysfunction monolayer mortality multicatalytic endopeptidase complex oral cavity epithelium oral pathogen pathogen protein degradation response soft tissue

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项目摘要

DESCRIPTION (provided by applicant): Human immunodeficiency virus (HIV) infects millions of humans annually and is a leading cause of death worldwide. In the absence of medical therapy, death usually results within 10 years of infection. The introduction of antiretroviral (ART) drugs has significantly diminished morbidity and mortality. However, ART must be taken throughout life, and the several long term effects (e.g. dyslipidemia, mitochondrial dysfunction, exocrine pathology) have only recently been appreciated. Studies that address the adverse effects of ART on the oral mucosa are lacking. Our goal is to elucidate the effects of ART on the function of oral soft tissues, focusing on epithelial cell biology. This knowledge is a requisite for understanding the long-term implications of ART on the critical importance of the mucosa and epithelium in controlling oral opportunistic infections in HIV infected individuals. The GENERAL HYPOTHESIS of the proposed research is select ART drugs dysregulate oral epithelial cell biology, impacting on normal proteasome pathways, epithelial cell homeostasis, and parameters of innate immunity, resulting in deleterious alternations of the oral mucosa and the epithelial cell's ability to respond to microbial pathogens. Our specific aims are to 1) examine the effect of ART on the proteasome-proteolytic pathway in oral epithelial cells, 2) determine the effects of ART on toll-like receptor (TLR) signaling pathways in oral epithelial cells, and 3) determine the effects of ART on oral epithelial cell differentiation. Specific biochemical and molecular methodologies are described that will allow us to systematically determine if ART adversely effects the proteasome function, TLR signaling and ability of epithelial cells to differentiate. These processes are key to maintaining oral mucosal health in patients who are infected with HIV and for understanding how opportunistic infections develop despite the presence of ART.

描述（由申请人提供）：人类免疫缺陷病毒（HIV）每年感染数百万人类，是全球死亡的主要原因。在没有药物治疗的情况下，死亡通常在感染后的10年内导致死亡。抗逆转录病毒（ART）药物的引入显着降低了发病率和死亡率。但是，必须在整个生命中采取艺术，并且直到最近才欣赏了几种长期影响（例如血脂异常，线粒体功能障碍，外分泌病理学）。缺乏解决艺术对口腔粘膜不利影响的研究。我们的目标是阐明艺术对口腔软组织功能的影响，重点是上皮细胞生物学。这些知识是理解艺术对粘膜和上皮在控制艾滋病毒感染个体口腔机会感染的重要重要性的长期意义的必要条件。拟议的研究的一般假设是精选的ART药物失调的口服上皮细胞生物学，影响正常的蛋白酶体途径，上皮细胞稳态以及先天免疫的参数，从而导致口服粘膜和上皮细胞对微生物疗法的能力做出有害的交替。我们的具体目的是1）检查ART对口腔上皮细胞中蛋白酶体蛋白溶解途径的影响，2）确定ART对口腔上皮细胞中Toll样受体（TLR）信号通路的影响，以及3）确定ART对口腔上皮细胞分化的影响。描述了特定的生化和分子方法论，这将使我们能够系统地确定艺术是否不利影响蛋白酶体功能，TLR信号传导和上皮细胞分化的能力。这些过程是维持感染艾滋病毒的患者口服粘膜健康的关键，并了解尽管存在艺术，但有机会感染如何发展。