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Role of alveolar macrophage in omega-3 fatty acid amelioration of silica-triggered autoimmunity.

肺泡巨噬细胞在 omega-3 脂肪酸改善二氧化硅引发的自身免疫中的作用。

基本信息

批准号：
10586303
负责人：
James J Pestka
金额：
$ 58.13万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2027-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10586303
关键词：
Acceleration Acids Acute Affect Alveolar Alveolar Macrophages American Autoantibodies Autoantigens Autoimmune Diseases Autoimmunity C57BL/6 Mouse Cathepsins Cell Death Cessation of life Chemosensitization Clinical Clustered Regularly Interspaced Short Palindromic Repeats Consumption DNA Data Development Diet Dietary Fats Dietary Fatty Acid Docosahexaenoic Acids Docosahexaenoic acid supplementation Dose Eicosanoids Embryo Environment Environmental Risk Factor Excision Exposure to Farm Fatty Acids Female Fetal Liver Fish Oils Fishes Flare Gene Expression Genome Glomerulonephritis Goals Grant Health Heredity Human Immune Tolerance Immunotherapy In Vitro Individual Infectious Agent Inflammation Inflammation Mediators Inflammatory Interferons Interleukin-1 Interleukin-1 alpha Interleukin-1 beta Link Lipids Liver Lung Lupus Lymphoid Tissue Lysosomes Macrophage Military Personnel Minerals Mining Mission Modeling Mus National Institute of Environmental Health Sciences Natural Immunity Omega-3 Fatty Acids Omega-6 Fatty Acids Pathway interactions Phagocytes Phenotype Planet Earth Play Population Predisposing Factor Production Quartz Risk Risk Factors Role Rupture Severities Silicon Dioxide Systemic Lupus Erythematosus Testing Tissues Toxic Environmental Substances United States National Institutes of Health Water adaptive immunity autoimmune rheumatologic disease cytokine dietary dietary supplements disability early onset environmental stressor fatty acid supplementation genetic signature human disease immunogenic immunogenic cell death in vivo insight lipidome manufacture mouse model novel particle pre-clinical prevent respiratory response self-renewal stressor systemic autoimmunity tool toxicant

项目摘要

Summary: "Role of Alveolar Macrophage in Omega-3 Fatty acid Amelioration of Silica-Triggered Autoimmunity” While heredity is a primary predisposing factor for autoimmunity, cumulative exposures to environmental factors such as toxic stressors and diet greatly impact latency and severity autoimmune diseases such as lupus. Our goal is to understand how lupus triggering by an ubiquitous environmental toxicant can be prevented by dietary modulation of cellular lipids. This goal is predicated on preliminary studies revealing that 1)airway exposure to crystalline silica, a recognized autoimmune disease risk factor, triggers early onset of systemic autoimmunity and glomerulonephritis in the lupus-prone female NZBWF1 mouse and 2)supplementing their diets with the omega-3 fatty acid docosahexaenoic acid (DHA), a well-known dietary supplement extracted from cold-water fish, dose-dependently blocks this triggering. Here, we will employ in vitro, ex vivo, and in vivo approaches to test the hypothesis that DHA consumption prevents silica- triggered autoimmunity by suppressing inflammatory mediator production, death, and self-antigen release in alveolar macrophages of NZBWF1 mice. Revealing DHA mechanisms against silica- triggered lupus will bring novel insights into how respiratory toxicants initiate lupus and subsequent flaring via lung as well as how manipulating cellular lipids through diet can be exploited to prevent environmental triggering of human autoimmune disease.

总结：“肺泡巨噬细胞在二氧化硅触发的Omega-3脂肪酸改善中的作用” 自身免疫” 虽然遗传是自身免疫的主要诱发因素，但累积暴露于环境因素，如毒性应激源和饮食，极大地影响潜伏期和严重程度自身免疫性疾病如狼疮。我们的目标是了解狼疮是如何由普遍存在的环境毒物可以通过调节细胞脂质的饮食来预防。这目标是预测初步研究表明，1）气道暴露于结晶二氧化硅，公认的自身免疫性疾病危险因素，触发全身性自身免疫性的早期发作，肾小球肾炎的狼疮倾向的雌性NZBWF 1小鼠和2）补充他们的饮食 ω-3脂肪酸二十二碳六烯酸（DHA），一种众所周知的膳食补充剂从冷水鱼中提取，剂量依赖性地阻止这种触发。在这里，我们将雇用在体外、离体和体内方法来检验DHA消耗防止二氧化硅- 通过抑制炎症介质的产生、死亡和自身抗原而引发自身免疫在NZBWF 1小鼠的肺泡巨噬细胞中释放。揭示DHA对抗二氧化硅的机制- 引发狼疮将带来新的见解如何呼吸毒物引发狼疮，以及如何通过饮食操纵细胞脂质，用于防止环境触发人类自身免疫性疾病。