Mitochondrial RNA as a proinflammatory mediator

线粒体 RNA 作为促炎介质

• 批准号: 10645222
• 负责人: DANA R CRAWFORD
• 金额: $ 8.15万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-14 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10645222
• 关键词: Blood; CCL2 gene; Cause of Death; Cells; Cerebral Edema; Chloroquine; Cytoplasm; Dendritic Cells; Detection; Diagnosis; Diagnostic; Disease; Double-Stranded RNA; Endosomes; Etiology; Foundations; Future; Goals; Healthcare; Human; Immune response; Immunologic Adjuvants; Immunologic Stimulation; In Vitro; Inflammation; Inflammation Mediators; Inflammatory; Injury; Interferons; Interleukin-10; Interleukin-6; Literature; Macrophage; Mitochondria; Mitochondrial DNA; Mitochondrial RNA; Molecular; Mus; Nucleic Acids; Oxidants; Oxidation-Reduction; Pathogenesis; Pathology; Pathway interactions; Pattern; Plasma; Prevention; RNA; RNA Binding; RNA Degradation; Receptor Signaling; Regulation; Ribonuclease III; Ribonucleases; Role; Signal Pathway; Specificity; Stroke; TNF gene; Testing; Transforming Growth Factor beta; United States; comparative; cost; exosome; extracellular; extracellular vesicles; in vivo; insight; lung injury; mouse model; oxidation; receptor; receptor binding; therapeutic target

Inflammation is implicated in a wide range of disorders and thought to be involved in most leading causes of death today in the United States with high associated costs. New insights into better understanding its etiology, detection and prevention are thus of major importance in health care. This has been achieved in part through the recent discovery of proinflammatory DAMPs, including mitochondrial DNA (mtDNA). However, little is known about the proinflammatory effects of the other major mitochondrial nucleic acid, mtRNA. Here, we propose to fill this gap by extending our recent mtRNA studies and assessing therapeutic targets. These studies are a major extension of a previously small literature on mtRNA immunostimulation, and provide new insights into the role of native and oxidized mtRNA in inflammation as a result of their inappropriate release to the cytoplasm and extracellular milieu including blood. Specifically, we propose to test the hypothesis that both native and oxidized mtRNAs are important inflammatory mediators with diagnostic and treatment potential. Here, we will characterize the mechanistic basis underlying the proinflammatory activity of mitochondrial RNA (mtRNA); determine the mechanistic effect of oxidation on mtRNA immunostimulation; and assess the immunostimulatory activity and associated structural forms of mtRNA in human plasma. The overall goal is to better understand the role of both native and oxidized forms of mtRNA in inflammation, and to eventually exploit this information toward the diagnosis and treatment of excessive mtRNA release-related inflammatory pathologies.

炎症与多种疾病有关，被认为是大多数主要原因