Chronic in vivo overexpression of TGF-B|1 using a retroviral expression vector

Abstract

There are numerous causes of progressive pulmonary fibrosis but the most common form is called idiopathic pulmonary fibrosis (IPF). The etiology of IPF is unknown and it is relentless and lethal. The proposed pathogenesis of IPF is that following tissue injury there is recruitment of inflammatory cells that are activated to release proinflammatory and fibrogenic cytokines. Of these cytokines TGF-$\beta\sb1$ is not only a mitogen for immature fibroblasts but also a chemoattractant for fibroblasts and induces connective tissue synthesis which leads to fibrosis. In an early pulmonary injury response TGF-$\beta\sb1$ is aberrantly present in alveolar macrophages. However, in progressive pulmonary fibrosis where there are advanced lesions, TGF-$\beta\sb1$ is present in alveolar macrophages and epithelial cells irrespective of the etiology. Although we have demonstrated that increased expression of TGF-$\beta\sb1$ by alveolar macrophages is important for the pathogenesis of pulmonary inflammation and fibrosis, we sought to determine if aberrant expression of TGF-$\beta\sb1$ by alveolar epithelial cells was also important in regulating the inflammation and fibrosis. (Abstract shortened by UMI.)