Characterizing the role of viral microRNAs in regulating macrophage plasticity

表征病毒 microRNA 在调节巨噬细胞可塑性中的作用

• 批准号: 9316850
• 负责人: Afsar Raza Naqvi
• 金额: $ 23.99万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316850
• 关键词: Actinobacillus actinomycetemcomitans; Address; Anti-Inflammatory Agents; Apoptosis; Binding; Biological Assay; Biological Process; Biological Response Modifiers; Biopsy; Categories; Cell Differentiation process; Cell Proliferation; Cell physiology; Cells; Code; Cytomegalovirus; Data; Defect; Dental Pulp; Dentistry; Development; Disease; Doctor of Philosophy; Eukaryota; Exhibits; Extracellular Matrix; Family; Gene Expression; Gene Targeting; Generations; Gingiva; Herpesviridae; Herpesviridae Infections; Herpesvirus 1; Human; Human Characteristics; Human Herpesvirus 8; Immune; Immune Evasion; Immune response; Immunologic Surveillance; Impairment; Infection; Inflammation; Inflammatory; Innate Immune Response; Knowledge; Life; Matrix Metalloproteinases; Mediating; Mediator of activation protein; Medicine; Membrane; Messenger RNA; MicroRNAs; Microbe; Mouth Diseases; Mucosal Immunity; Myelogenous; Myeloid Cells; Nitrogen; Nucleotides; Oral; Oral cavity; Oral mucous membrane structure; Outcome; Oxygen; Pathogenesis; Pathway interactions; Patients; Phenotype; Play; Polyamines; Population; Porphyromonas gingivalis; Prevention; Production; Recruitment Activity; Recurrence; Resolution; Role; Sampling; Signal Transduction; Site; Sorting - Cell Movement; Surface; Tissues; Tooth Diseases; Transcript; Translations; Tropism; Untranslated RNA; Viral; Virus; Virus Diseases; Wound Healing; base; beta-Defensins; cell motility; conditioning; cytokine; differential expression; exosome; immune activation; immunoregulation; inhibitor/antagonist; insight; keratinocyte; latent infection; macrophage; member; migration; monocyte; nanovesicle; novel; novel therapeutic intervention; pathogen; periopathogen; response; seropositive; therapeutic target; transcriptome

Characterizing the role of viral microRNAs in regulating macrophage plasticity Afsar Raza Naqvi, Ph.D. Emerging evidences show implication of human herpesviruses (HHV) infection in oral inflammatory diseases. These viruses establish lifelong infection which requires immune evasion. HHV, like eukaryotes, encode microRNAs (miRNA) which are non-protein coding regulatory RNAs. MiRNAs binds to and silence target gene expression thereby controlling various biological processes including cell differentiation, apoptosis, immune responses, etc. Viral miRNAs (vmiRs) play critical role in pathogenesis as they can regulate expression of both virus and host derived transcripts. In our preliminary studies, we identified induced levels of several vmiRs in biopsies from patients with inflamed pulps or diseased gingiva. Macrophages (Mφ) are important component of immune surveillance in oral mucosa. Depending on the activation status, Mφ are categorized as classical proinflammatory (M1) and alternative antiinflammatory (M2). We aim to characterize the role of our previously identified candidate vmiRs in regulating Mφ plasticity through modulation of host miRNAs. The impact of vmiR mediated differential expression of cellular and exosomal miRNA profiles of M1 and M2 Mφ will be assessed. VmiR mediated functional modulation of Mφ plasticity will be assessed by examining phenotype associated markers. This aspect has not been investigated earlier and will likely provide novel insights on the role of vmiR in the pathogenesis of oral diseases. Dynamic interaction of myeloid cells with surrounding oral keratinocytes is required to amplify innate immune responses for a favorable outcome. The effect of exosomes derived from vmiR expressing M1 and M2 Mφ will be examined on key biological functions of primary human oral keratinocytes including innate immune responses, cell proliferation and migration. The data generated will provide significant information to address existing knowledge gaps. Importantly, as vmiRs are not endogenous RNAs, they have the potential to be deployed as potential therapeutic targets.

表征病毒microRNA在调节巨噬细胞可塑性中的作用 Afsar Raza Naqvi博士 越来越多的证据表明人类疱疹病毒（HHV）感染与口腔炎症性疾病有关。 这些病毒建立终身感染，需要免疫逃避。HHV和真核生物一样， microRNA（miRNA）是一种非蛋白质编码的调控RNA。miRNAs结合并沉默靶基因 表达，从而控制各种生物学过程，包括细胞分化、凋亡、免疫调节、免疫调节、免疫调节、免疫调节和免疫调节。 病毒miRNAs（vmiRs）在致病机制中起着关键作用，因为它们可以调节两种基因的表达， 病毒和宿主衍生的转录物。在我们的初步研究中，我们确定了几种vmiR的诱导水平， 从牙髓发炎或牙龈患病的病人身上取活检。巨噬细胞（Mφ）是细胞的重要组成部分， 口腔粘膜免疫监视根据激活状态，Mφ被归类为经典的 促炎（M1）和替代性炎症（M2）。我们的目标是描述我们以前的角色 鉴定了通过调节宿主miRNAs调节Mφ可塑性的候选vmiRs。vmiR的影响 将评估M1和M2 Mφ的细胞和外泌体miRNA谱介导的差异表达。 将通过检查与VmiR介导的Mφ可塑性相关的表型来评估VmiR介导的Mφ可塑性功能调节。 标记。这方面的研究还没有早期，并可能提供新的见解的作用vmiR 在口腔疾病的发病机制中的作用。骨髓细胞与周围口腔角质形成细胞的动态相互作用 是增强先天免疫反应以获得有利结果所必需的。来源于以下的外来体的作用 将检测表达M1和M2 Mφ的vmiR对原代人口腔黏膜上皮细胞的关键生物学功能的影响。 角质形成细胞包括先天免疫应答、细胞增殖和迁移。生成的数据将 提供重要信息以解决现有的知识差距。重要的是，由于vmiR不是内源性的， RNA，它们有可能作为潜在的治疗靶点。