Increased TGF-b1* in the Lungs of Asbestos-Exposed Rats and Mice: Reduced Expression in TNF-a Receptor Knockout Mice
- 1 January 2001
- journal article
- Published by Begell House in Journal of Environmental Pathology, Toxicology and Oncology
- Vol. 20 (2) , 12
- https://doi.org/10.1615/jenvironpatholtoxicoloncol.v20.i2.30
Abstract
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-b1) 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-b1 is rapidly expressed postexposure at sites of initial asbestos-induced lung injury in both rats and mice. The TGF-b1 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-b1, as we have demonstrated previously for PDGF-A and -B, TGF-a, and TNF-a. TGF-b1 expression is accompanied by collagen and fibronectin production in asbestos-exposed animals. Most interesting, TGF-b1 expression is largely absent in the lungs of TNF-a receptor knockout mice that fail to develop asbestos-induced IPF.We have shown previously that the mRNAs and cognate peptides of PDGF-A and -B and TGF-a, but not TNF-a, are reduced in the fibrosis-resistant knockout mice. In this article, we show that TGF-b1 is included in this group of cytokines, supporting the postulate that TNF-a is necessary for the expression of other, more downstream growth factors, and the consequent development of idiopathic pulmonary fibrosis (IPF).Keywords
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