Asbestos-induced peptide growth factors that mediate interstitial pulmonary fibrosis

Background. Using immunohistochemistry and in situ hybridization, we are studying the expression of growth factors at sites of initial lung injury in genetically defined mice. The purpose of these studies was to establish which of the many cytokines released during lung injury and repair play an essential role in mediating interstitial fibrogenesis. Methods. We identified two mouse strains that were resistant to the fibrogenic effects of inhaled asbestos fibers, the 129 strain and an F2 hybrid of a C57BL/6 cross with the 129 strain. If we found that the expression of specific growth factors was altered in these animals, it may then be possible to determine whether a given factor is central to the development of asbestos-induced fibroproliferative disease. Results. Thus, we found that the 129 mouse strain exhibited significantly reduced expressions of TGF-beta, and TNF-alpha, whereas mice with both receptors for TNF-a knocked out had reduced levels of PDGF-A and TGF-alpha. Conclusions. Now we can focus on these growth factors as potential mediators of fibrogenic lung disease.