Role of mitogen-activated protein kinases (MAPK) in cell injury and proliferation by environmental particulates.

Cell signaling pathways may be initiated by environmental particulates by indirect mechanisms such as elaboration of reactive oxygen or nitrogen species (ROS/RNS) or directly upon contact of particulates with the plasma membrane and uptake by epithelial or mesothelial cells. Research in the last few years has mainly addressed cell signaling cascades leading to activation of the redox-sensitive transcription factors, nuclear factor kappa-B (NF-kappaB), and activator protein-1 (AP-1). The activation of these transcription factors may be linked to increases in gene expression controlling cell injury or apoptosis, proliferation and/or cell survival, and inflammatory cytokines. Here, we provide an overview of the MAPK signaling pathways and their activation by asbestos, specifically the role of ROS, receptor-dependent and independent activation via the epidermal growth factor receptor (EGFR), and strategies for proving causal relationships between these pathways and changes in epithelial cell phenotype linked to disease causation.