Dietary Lipids and Silica-Accelerated Autoimmunity

膳食脂质和二氧化硅加速自身免疫

基本信息

批准号：
8469038
负责人：
James J Pestka
金额：
$ 15.04万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-11 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8469038
关键词：
Acceleration Adult Affect American Antibody Formation Apoptosis Area Asbestos Autoantigens Autoimmune Diseases Autoimmune Process Autoimmunity Centers for Disease Control and Prevention (U.S.)Chemoprevention Chemosensitization Chronic Clinical Research Consumption Development Diet Dietary Factors Dietary Fats Disease Disease Progression Docosahexaenoic Acids Effectiveness Environmental Exposure Environmental Risk Factor Epidemiology Exposure to Fibrosis Fish Oils Food Foundations Funding Opportunities Gene Expression Genetic Transcription Glomerulonephritis Goals Health Heavy Metals Human Immune system Immunity Immunoglobulin A Indium Individual Industry Inflammation Inflammatory Inhalation Exposure Kidney Kidney Diseases Kidney Failure Knowledge Language Lead Leukocytes Life Style Link Lung Lung diseases Lupus Lupus Nephritis Mining Mission Modeling Mus National Institute of Allergy and Infectious Disease National Institute of Environmental Health Sciences Nephritis Nutritional Occupational Exposure Occupations Onset of illness Outcome Persons Pesticides Plasma Cells Polyunsaturated Fatty Acids Prevalence Prevention Production Public Health Recruitment Activity Recurrence Regimen Renal function Research Resolution Risk Severities Silicon Dioxide Supplementation Surveys Systemic Lupus Erythematosus Testing Tissues Toxicant exposure Trichloroethylene Trichothecenes United States National Institutes of Health Work abstracting base cytokine improved insight lupus prone mice macrophage mouse model preclinical study prevent research study toxicant

项目摘要

DESCRIPTION (provided by applicant): Autoimmune diseases, a constellation of chronic, disabling illnesses that result from the immune system attacking the body's own tissues, are estimated to adversely affect up to 25 million persons in the U.S. The prevalence of autoimmune diseases is markedly impacted by environmental factors (e.g. toxicant exposures) and lifestyle choices (e.g. diet). Notably, the risk of developing systemic lupus erythematosus (lupus), a prototypical autoimmune disease affecting 300,000 Americans and often associated with glomerulonephritis and kidney failure, is increased by occupational exposure (e.g. mining, construction, custodial and manufacturing industries) to silica. Research studies reveal that consumption of n-3 polyunsaturated fatty acids (PUFAs) found in fish oil holds promise for preventing and ameliorating chronic inflammatory diseases including autoimmune nephritis. The specific objective here is to test the hypothesis that consumption of n-3 PUFAs will suppress silica-accelerated nephritis in lupus-prone mice and that this will correspond with decreased leukocyte recruitment and inflammation-associated gene expression in the kidney. This research will be accomplished in two aims. In Aim 1, n-3 PUFA consumption and how it affects latency and severity of silica-accelerated lupus nephritis will be established. In Aim 2, a determination of how n-3 PUFA modulates progression of existing silica-accelerated lupus nephritis will be tested. Consistent with the NIEHS mission, the expected outcomes of these aims will be an increased understanding of how n-3 PUFAs impact silica triggering and exacerbation of autoimmune nephritis. These findings will have a positive impact, because it will be an initial step in the path to predicting how n-3 PUFA consumption might prevent or ameliorate acceleration of autoimmunity by silica and other toxicants. The contribution of this research is expected to be an improved understanding of how n-3 PUFA consumption counteracts the triggering and exacerbation of lupus nephritis by silica. This contribution is significant because it will be the first step in a research continuum that will lead to nutritional strategies to mitigate environmental triggering and exacerbation of autoimmunity. Availability of such preventative and ameliorative strategies would enable individuals who are occupationally exposed to silica to 1) reduce their risk for developing lupus and other autoimmune disease and 2) delay progression of existing autoimmunity by increasing n-3 PUFA consumption via diet and/or supplementation. Furthermore, n-3 PUFA chemoprevention and chemointervention might similarly be applied to workers who are at increased risk of autoimmunity from exposures to toxicants such as asbestos, heavy metals, trichloroethylene, and pesticides. Finally, it is expected that these studies will reveal additional potential benefits of n-3 PUFA consumption on silica-induced lung disease and fibrosis, another understudied area.

描述（由申请人提供）：自身免疫性疾病是由免疫系统攻击人体自身组织引起的一系列慢性致残性疾病，据估计对美国多达 2500 万人产生不利影响。自身免疫性疾病的患病率受到显着影响受环境因素（例如有毒物质暴露）和生活方式选择（例如饮食）的影响。值得注意的是，患系统性红斑狼疮 (狼疮) 是一种典型的自身免疫性疾病，影响 30 万美国人，通常与肾小球肾炎和肾衰竭有关，职业接触二氧化硅（例如采矿、建筑、保管和制造行业）会增加患系统性红斑狼疮 (狼疮) 的风险。研究表明，食用鱼油中的 n-3 多不饱和脂肪酸 (PUFA) 有望预防和改善包括自身免疫性肾炎在内的慢性炎症性疾病。这里的具体目标是检验以下假设：摄入 n-3 PUFA 会抑制狼疮易发小鼠的二氧化硅加速肾炎，并且这与肾脏中白细胞募集和炎症相关基因表达的减少相对应。这项研究将实现两个目标。在目标 1 中，将确定 n-3 PUFA 的消耗量及其如何影响二氧化硅加速狼疮性肾炎的潜伏期和严重程度。在目标 2 中，将测试 n-3 PUFA 如何调节现有二氧化硅加速狼疮肾炎的进展。与 NIEHS 的使命一致，这些目标的预期成果将是加深对 n-3 PUFA 如何影响二氧化硅引发和恶化自身免疫性肾炎的了解。这些发现将产生积极影响，因为这将是预测 n-3 PUFA 消耗如何预防或改善二氧化硅和其他毒物加速自身免疫的第一步。这项研究的贡献预计将有助于更好地了解 n-3 PUFA 消耗如何抵消二氧化硅引发和恶化的狼疮性肾炎。这一贡献意义重大，因为它将是导致营养学研究连续体的第一步减轻环境触发和自身免疫恶化的策略。这种预防和改善策略的可用性将使职业接触二氧化硅的个人能够 1) 降低患狼疮和其他自身免疫性疾病的风险，以及 2) 通过饮食和/或补充剂增加 n-3 PUFA 消耗来延缓现有自身免疫性疾病的进展。此外，n-3 PUFA 化学预防和化学干预可能同样适用于因接触石棉、重金属、三氯乙烯和农药等有毒物质而面临自身免疫风险增加的工人。最后，预计这些研究将揭示 n-3 PUFA 消耗对二氧化硅引起的肺病和纤维化的额外潜在益处，这是另一个尚未研究的领域。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse.

DOI：
10.1371/journal.pone.0125481
发表时间：
2015
期刊：
PloS one
影响因子：
3.7
作者：
Bates MA;Brandenberger C;Langohr I;Kumagai K;Harkema JR;Holian A;Pestka JJ
通讯作者：
Pestka JJ

Silica-Triggered Autoimmunity in Lupus-Prone Mice Blocked by Docosahexaenoic Acid Consumption.

DOI：
10.1371/journal.pone.0160622
发表时间：
2016
期刊：
PloS one
影响因子：
3.7
作者：
Bates MA;Brandenberger C;Langohr II;Kumagai K;Lock AL;Harkema JR;Holian A;Pestka JJ
通讯作者：
Pestka JJ