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

摘要：《肺泡巨噬细胞在二氧化硅触发的欧米茄-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易感因素，但累积暴露于 环境因素，如中毒应激源和饮食，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通过 无处不在的环境毒物可以通过饮食调节细胞脂来预防。这 Goal是基于初步研究表明：1)接触结晶二氧化硅的呼吸道，a) 公认的自身免疫性疾病危险因素，触发早期系统性自身免疫和 狼疮易感雌性NZBWF1小鼠的肾小球肾炎及2)补充饲料 欧米茄-3脂肪酸二十二碳六烯酸(DHA)，一种著名的膳食补充剂 从冷水鱼中提取，剂量依赖地阻止这种触发。在这里，我们将在 体外、体外和体内方法，以检验DHA摄取防止二氧化硅- 通过抑制炎症介质的产生、死亡和自身抗原来触发自身免疫 NZBWF1小鼠肺泡巨噬细胞释放。揭示DHA抗二氧化硅的机理-- 触发的狼疮将为呼吸道毒素如何引发狼疮和 随后通过肺的燃烧，以及如何通过饮食来操纵细胞脂 被用来防止环境触发人类自身免疫性疾病。

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.