Akt activation sustains silica induced inflammation

Akt 激活维持二氧化硅诱导的炎症

• 批准号: 6892908
• 负责人: CELINE A BEAMER
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6892908
• 关键词: alveolar macrophages; apoptosis; biological signal transduction; enzyme activity; genetic transcription; genetically modified animals; inflammation; laboratory mouse; leukocyte activation /transformation; nuclear factor kappa beta; pneumoconiosis; postdoctoral investigator; serine threonine protein kinase; silicates; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): Silicosis is an occupational lung disease resulting from the inhalation of silica particles which causes chronic inflammation and progressive pulmonary fibrosis. Phagocytosis of inhaled silica particles by alveolar macrophages (AM) and subsequent activation of AM is a crucial step in the pathogenesis of silicosis; however, the participation of specific intracellular signaling pathways in regulating this process remains largely unknown. The goal of this study is to test the central hypothesis that silica induced production of TNF alpha sustains inflammation by activating the Akt signaling pathway in AM. The specific aims of this proposed research are: 1) to assess the cellular fate of AM following exposure to silica, 2) to determine the effects of silica on the Akt signaling pathways in AM, and 3) to elucidate the ability of silica induced TNF alpha production to stimulate the Akt signaling pathway and alter call fate (apoptosis vs. survival). Defining the function of this signaling pathway in regulating AM activation and cell fate is of interest because a better understanding of the molecular events involved may permit targeting of key biochemical pathways for more effective diagnosis and treatment of occupational lung diseases.

描述（由申请人提供）：硅化是一种职业肺部疾病，是由于吸入二氧化硅颗粒而引起的，导致慢性炎症和进行性肺纤维化。通过肺泡巨噬细胞（AM）对吸入的二氧化硅颗粒的吞噬作用和随后的AM激活是有机疾病发病机理的关键步骤。然而，特定细胞内信号通路参与调节这一过程仍然未知。这项研究的目的是检验中心假设，即二氧化硅诱导的TNFα的产生通过激活AM中的AKT信号通路来承受炎症。这项拟议的研究的具体目的是：1）评估暴露于二氧化硅后AM的细胞命运，2）确定二氧化硅对AM中AKT信号通路的影响，以及3）阐明二氧化硅引起的TNF Alpha产生的能力，以刺激AKT信号途径和刺激呼叫命运（Apoptistosis vs. apoptosis Vs. vs. vs. vs. vs. vs. vs.定义该信号通路在调节AM激活和细胞命运方面的功能引起了人们的关注，因为对所涉及的分子事件的更好理解可能允许靶向关键的生化途径，以更有效地诊断和治疗职业肺部疾病。