Cellular and molecular mechanisms of asbestos-induced fibrosis

Pleural and pulmonary fibrosis (asbestosis) are ramifications of occupation al exposures to asbestos fibers, a diverse family of ubiquitous, naturally- occurring minerals. The pathogenesis of asbestos-associated fibrosis involv es the participation of a number of cell types and is characterized by an e arly and persistent inflammatory response that involves the generation of o xidants, growth factors, chemokines, and cytokines. These mediators may als o contribute directly to cell injury, proliferation, and fibrogenesis. Afte r interaction with cells, asbestos fibers trigger a number of signaling cas cades involving mitogen-activated protein kinases(MAPK) and nuclear factor kappa-8 (NF-kappa B). Activation of transcription factors such as NF-kappa B and activator protein-1 (AP-1) may be linked to increases in early respon se genes (e.g., c-jun and c-fos) which govern proliferation, apoptosis, and inflammatory changes in the cells of the lung. The goal of this article is to review the cellular and molecular mechanisms of asbestos-induced fibros is that may be critical to the development of effective treatment regimens. (C) 1999 Wiley-Liss, Inc.