Role of Matrix Metalloproteinase-3 in Deployment-Related Pulmonary Fibrosis

Abstract

We have demonstrated that exposure of mice to silicate-containing PM induces pulmonary fibrosis with initial inflammation in the terminal bronchioles and alveolar ducts followed by collagen deposition. We have demonstrated that human alveolar macrophages respond to inhaled particulate matter by producing an array of inflammatory and fibrogenic mediators that likely contribute to the respiratory symptoms and clinical illness frequently observed in military personnel previously deployed to Southwest Asia and Afghanistan. We have demonstrated the feasibility of engineering highly selective TIMP-based MMP inhibitors by yeast surface display. We expect this result to impact the field of protein engineering. Our efforts to uncover the sequence and structural determinants responsible for improvements in TIMP-1 selectivity will also impact the understanding of protein-protein interactions and binding specificity.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2020
Accession Number
AD1145728

Entities

People

  • Derek C. Radisky
  • Gregory P. Downey

Organizations

  • National Jewish Health

Tags

DTIC Thesaurus Topics

  • Air Force
  • Air Force Facilities
  • Asia
  • California
  • Department Of Defense
  • Deployment
  • Diseases And Disorders
  • Engineering
  • Health Services
  • Lung Diseases
  • Macrophages
  • Mass Spectrometry
  • Medical Personnel
  • Military Personnel
  • Particulate Matter
  • Southwest Asia
  • United States

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Mental Health of Military Veterans with Posttraumatic Stress Disorder (PTSD): Risk Factors, Prevalence, Symptoms, and Treatment.
  • Molecular Biology and Genetics

Technology Areas

  • Biotechnology