Cell signaling and transcription factor activation by asbestos in lung injury and disease.
Signaling pathways initiated at the external cell surface or within the cytoplasm regulate transactivation of transcription factors and gene expression that are causally related to a number of critical cellular outcomes including proliferation, apoptosis, cell survival, and production of inflammatory cytokines. Asbestos, a ubiquitous pathogenic group of mineral fibers, can stimulate gene expression in a variety of cell types in the lung via intracellular signaling pathways. These cell signaling cascades may be initiated through receptor-mediated events or integrins. Alternatively, they may be stimulated by oxidants generated both during phagocytosis of minerals and/or by redox reactions on the mineral surface. Once initiated, these pathways can lead to promotion of gene expression critical to cellular injury, proliferation and inflammation-events leading to the development of fibroproliferative diseases of the lung and pleura. The elucidation and relevance of critical signaling cascades to lung injury or repair following asbestos exposure could aid in developing strategies to prevent or treat asbestos-associated lung and pleural diseases.
Shukla
Arti
A
Department of Pathology, University of Vermont College of Medicine, 89 Beumont Avenue, Burlington 05405, USA.
Ramos-Nino
Maria
M
Mossman
Brooke
B
D000818:Animals; D001194:Asbestos / Q000737:chemistry / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008654:Mesothelioma / Q000209:etiology / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010997:Pleural Neoplasms / Q000209:etiology / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
D001194:Asbestos; D002118:Calcium; D020929:Mitogen-Activated Protein Kinase Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D018808:Transcription Factor AP-1; D000097782:NF-kappaB-Inducing Kinase