Increased TGF-beta1 in the lungs of asbestos-exposed rats and mice: reduced expression in TNF-alpha receptor knockout mice.

Inhalation of numerous fibrogenic agents causes interstitial pulmonary fibrosis (IPF) in humans and in a number of animal models. Several of these models provide evidence that certain peptide growth factors (GF) are playing a role in the disease process. Transforming growth factor beta 1 (TGF-beta1) is a potent inducer of extracellular matrix production by mesenchymal cells, and we have shown that this peptide is produced in the lung after asbestos exposure. We used in situ hybridization to demonstrate that the mRNA for TGF-beta1 is rapidly expressed post-exposure at sites of initial asbestos-induced lung injury in both rats and mice. The TGF-beta1 is expressed by bronchiolar-alveolar epithelial cells as well as by mesenchymal cells and lung macrophages in exposed animals. Normal rats and mice express little TGF-beta1, as we have demonstrated previously for PDGF-A and -B, TGF-alpha, and TNF-alpha. TGF-beta1 expression is accompanied by collagen and fibronectin production in asbestos-exposed animals. Most interesting, TGF-beta1 expression is largely absent in the lungs of TNF-alpha receptor knockout mice that fail to develop asbestos-induced IPE We have shown previously that the mRNAs and cognate peptides of PDGF-A and -B and TGF-alpha, but not TNF-alpha, are reduced in the fibrosis-resistant knockout mice. In this article, we show that TGF-beta1 is included in this group of cytokines, supporting the postulate that TNF-alpha is necessary for the expression of other, more downstream growth factors, and the consequent development of idiopathic pulmonary fibrosis (IPF).