| 研究実績の概要 |
1. Respiratory disease like Chronic Obstructive Pulmonary Disease (COPD) and silicosis show irreversible inflammation and disease progression, leading frequently to death. This happens even if exposure to the trigger (tobacco smoke for COPD and silica for silicosis) is eliminated. The goal of this project is to understand the mechanisms leading to irreversible inflammation in a silicosis model.
2. We expose mice to different amounts of silica for one month, then monitor the progression of the disease in the lungs over one year. We measure expression levels of inflammatory markers and the numbers of immune cells in the lungs at each time point. We also measure genome-wide changes in gene expression and transcription factor binding using next generation sequencing.
3. We found that mice exposed to silica once during the first month of the experiment have transient elevation in the expression of inflammatory genes that eventually returns to basal levels. However, mice exposed to four doses of silica during the first month show persistently elevated expression of inflammatory genes after one year. These mice show increased number of infiltrating T cells in the lungs. This effect is not explained by aging, which is instead associated with increased infiltration of neutrophils.
4. We will integrate the data from next generation sequencing with protein interactions, evolutionary conservation and additional prior information, to determine changes in transcriptional regulatory networks associated with the onset of irreversible inflammation.
|
