Teaching Specialty

Cytokine Biology, Pathobiology of the Pneumoconises

Laboratory Name

Lung Biology Group
J. Bennett Johnston Bldg.
Grant Support: NIH, Intramural

Phone: (504) 988-5225
Fax: (504) 988-5707

• Brody, Arnold R. Inhalation of asbestos fibers and consequent expression of peptide growth factors. Inhal. Toxicol. 12(suppl. 3):245-250, 2000.
  
  
• Liu, J.-Y. and Brody, A. R. Increased TGF-b1 in the lungs of asbestos-exposed rats and mice: Reduced expression in TNF-a receptor knockout mice. J. Environ. Pathol. Toxicol. Oncol. 20(2):97-108, 2001.
  
  
• Warshamana, G. S., Corti, M., and Brody, A. R. TNF-a, PDGF, and TGF-b1 expression by primary mouse lung bronchiolar-alveolar epithelial and mesenchymal cells: TNF-a, induces TGF-b1. Exp. Mol. Pathol. 71:13-33, 2001.
  

• Liu, J.-Y., Sime, P. J., Wu, T., Warshamana, G. S., Pociask, D., Tsai, S.-Y., and Brody, A. R. Transforming Growth Factor-b1 overexpression in Tumor Necrosis Factor-a receptor knockout mice induces fibroproliferative lung disease. Am. J. Respir. Cell Mol. Biol. 25:3-7, 2001.
  
  
• Hoyle, G. W., and Brody, A.R. IL-9 and Lung Fibrosis: A Th2 Good Guy. Am. J. Respir. Cell Mol. Biol. 24:365-367, 2001.
  
  
• Brass, D. M., Tsai, S.-Y., and Brody, A. R. Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness "in vitro." Exp. Lung Res. 27:639-653, 2001.
  
  
• Brody, A. R. Plusieurs voies pour la fibrose interstitielle pulmonaire? (Interstitial pulmonary fibrosis). Revue Internationale de Biologie et de Médecine (Intl. J. Biol. Med.), 17:1222, 2001.
  
  
• Warshamana, G. S., Pociask, D. A., Fisher, K. J., Liu, J.-Y., Sime, P. J., and Brody, A. R. Titration of non-replicating adenovirus as a vector for transducing active TGF-b1 gene expression causing inflammation and fibrogenesis in the lungs of C57BL/6 mice. Int. J. Exp. Path., 83:183-201, 2002.
  
  
• Warshamana, G. S., Pociask, D. A., Sime, P. J., Schwartz, D. A., and Brody, A. R.
  Susceptibility to asbestos-induced and TGF-b1-induced fibroproliferative lung disease in two strains of mice. Am. J. Respir. Cell Mol. Biol., 27:705-713, 2002.
  
  
• Lasky, J. A., Ortiz, L. A., and Brody, A. R. Chronic Lung Injury and Fibrosis: Potential Roles for TNF-a, PDGF, CTGF, and TGF-b. In: Lung Injury: Mechanisms, Pathophysiology, and Therapy. (Notter, R. H., Holm, B. A., Finkelstein, J. N., Eds.) Marcel Dekker, N.Y., 2003, In Press
  
  
  

Books

• Brody, D. E. and Brody, A. R. The Science Class You Wish You Had . . . The Seven Greatest Scientific Discoveries in History and the People Who Made Them.
  With a Foreword by Martin Rodbell, Ph.D., Nobel Prize Recipient. The Berkley Publishing Group, New York, NY, 378 pp, 1997.
  

Research ongoing in the laboratories of the Lung Biology Program is focused on the biochemical and molecular mechanisms that mediate fibroproliferative lung disease caused by inhaling environmental agents. This disease process results in lung scarring and afflicts millions of individuals worldwide. Lung damage results initially in cellular proliferation and progressive production of extracellular matrix components, the two hallmarks of pulmonary fibrosis. Multiple interacting cytokines must be mediating the disease process, but the precise factors involved have yet to be defined. We have focused on four peptide growth factors that are likely to serve as mediators of the scarring process: 1) Platelet-derived growth factor, 2) transforming growth factor alpha, 3) TGF-beta, and 4) tumor necrosis factor alpha. In an established model of asbestos-induced lung fibrosis in rats and mice, we have determined the patterns of initial gene expression at sites of lung injury by in situ hybridization and Northern analysis, and we have determined the concomitant appearance of the specific growth factor proteins by immunohistochemistry. Currently we are studying the role of these growth factors in genetically-defined mice that are resistant to the fibrogenic effects of inhaled asbestos. In our view, the use of transgenic and knockout mice hold the key to our understanding the roles of specific cytokines in the pathogenesis of environmental lung disease.

Recent Publications or Reports

• Liu, J.-Y., Brass, D. M., Hoyle, G. W., Brody, A. R. TNF-a receptor knockout mice are protected from the fibroproliferative effects of inhaled asbestos fibers. Am. J. Pathol. 153: 1839-1847, 1998.
  
  
• Liu, J.-Y., Lei, W.-H., Brody, A. R., Hoyle, G. W. Investigation of tissue preparation conditions for nonradioactive in situ hybridization: Localization of transforming growth factor-a message in rat kidney. Histochem. J. 30:793-798, 1998.
  
  
• Brass, D., Hoyle, G. W., Poovey, H.G., Liu, J.-Y., and Brody, A.R. Reduced TNF-a and TGF-b1 expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure. Am. J. Pathol. 154:853-862, 1999.
  
  
• Hoyle, G. W., Li, J., Finkelstein, J. B., Eisenberg, T., Liu, J.-Y., Lasky, J., Athas, Morris,G., and Brody, A. R. Emphysematous lesions, inflammation, and fibrosis in the lungs of transgenic mice overexpressing platelet-derived growth factor. Am. J. Pathol. 154:1763-1775, 1999.