Role of Matrix Metalloproteinase-3 in Deployment-Related Pulmonary Fibrosis
Abstract
Since the onset of military operations in Afghanistan in 2001 and Iraq in 2003 through Operations Iraqi Freedom, Enduring Freedom, and New Dawn (OIF/OEF/OND), more than 2.8 million military personnel, DoD contractors, US government, and NGO employees have been deployed to these regions. These personnel have been exposed to high levels of airborne particulate matter (PM; desert dust) generated by wind erosion of desert sand, movement of vehicles and troops, combustion and construction activities, and combat, with both short and long-term health consequences. In deployed military personnel, high levels of PM have been causally implicated in the observed increase in respiratory symptoms, asthma, bronchiolitis, and eosinophilic and interstitial lung disease. The goal of this application is to determine the mechanisms by which inhalational exposure to silicate-containing respirable PM during military deployment to Southwest Asia leads to chronic pulmonary inflammation and fibrosis and to investigate strategies to diagnose and repair this damage. Aim 1 is to determine the role of MMP-3 in preclinical (murine) models of pulmonary fibrosis induced by instillation of bleomycin, silica, or silicate-containing particulate matter (PM) from Iraq and Afghanistan. Aim 2 is to develop an MMP-3-selective Tissue Inhibitor of Metalloproteinase (TIMP) as therapeutic target for progressive pulmonary fibrosis using both in silico and in vitro approaches. Aim 3 is to determine if MMP-3 levels are elevated in the lungs and blood of patients with pulmonary fibrosis and in military personnel previously deployed to Southwest Asia and can be used as a biomarker for disease progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2020
- Accession Number
- AD1130916
Entities
People
- Derek Radisky
- Gregory P. Downey
Organizations
- Mayo Clinic