Inflammatory Injury Caused by Silica Exposure

项目摘要 在美国，有200多万人在工作中接触到可呼吸的结晶二氧化硅。吸入 含有可呼吸结晶二氧化硅的粉尘会引起矽肺，其特征是慢性 炎症和肺纤维化。接触二氧化硅也会增加罹患癌症的风险 自身免疫性疾病和癌症。矽肺患者中位生存期为6年 诊断。矽肺的病理生理学机制尚不完全清楚。目前，没有 对这种毁灭性疾病的有效治疗。据报道，监管失调 肺泡巨噬细胞的表达在矽肺的发病机制中起重要作用。这份证词 肺泡内细二氧化硅颗粒和肺泡巨噬细胞对二氧化硅颗粒的摄取触发 促炎和促纤维化反应。然而，该机制的分子机制 肺泡巨噬细胞反应失调仍难以捉摸。使用矽肺的小鼠模型， 我们的初步研究表明髓系HDAC6在发病机制中起重要作用。 死于矽肺病。在拟议的研究中，我们将检验髓系HDAC6是关键的假设 矽肺的促炎和促纤维化反应的介体。我们将调查 髓系HDAC6在矽肺中的特殊作用及评价其治疗潜力 治疗矽肺的靶点。

Project Summary More than 2 million people in the US are exposed to respirable crystalline silica at work. Inhalation of dust containing respirable crystalline silica causes silicosis, which is characterized by chronic inflammation and pulmonary fibrosis. Silica exposure also increases the risk of developing autoimmune diseases and cancer. Silicosis patients have a median survival of 6 years after diagnosis. The pathophysiology of silicosis has not been fully understood. Currently, there is no effective treatment against this devastating disease. It has been reported that the dysregulation of alveolar macrophages plays an important role in the pathogenesis of silicosis. The deposition of fine silica particles in alveoli and the ingestion of silica particles by alveolar macrophages trigger pro-inflammatory and pro-fibrotic responses. However, molecular mechanisms of the dysregulated alveolar macrophage responses remain elusive. Using a mouse model of silicosis, our preliminary studies indicate that myeloid HDAC6 plays an essential role in the pathogenesis of silicosis. In the proposed studies, we will test the hypothesis that myeloid HDAC6 is a key mediator of pro-inflammatory and pro-fibrotic responses in silicosis. We will investigate the specific role of myeloid HDAC6 in silicosis and evaluate the therapeutic potential of HDAC6 as a target to treat silicosis.