title: Ambient particulate matter causes activation of the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis in lung epithelial cells.
abstract: Numerous epidemiological studies have demonstrated a positive association between ambient air pollution and adverse health effects including respiratory morbidity, asthma, and lung cancer. It has been suggested in some experimental studies that airborne particulate matter (PM) can produce inflammatory effects, but nothing is known about the possible proliferative and carcinogenic effects of these particles on cells of the lung. We show here that exposure of pulmonary epithelial cells, a cell type affected in acute lung injury, asthma, and lung carcinomas, to nontoxic concentrations of PM in vitro results in increases in c-jun kinase activity, levels of phosphorylated cJun immunoreactive protein, and transcriptional activation of activator protein-1-dependent gene expression. These changes are accompanied by elevations in numbers of cells incorporating 5'-bromodeoxyuridine, a marker of unscheduled DNA synthesis and/or cell proliferation. Data here are the first to demonstrate that interaction of ambient PM with target cells of the lung initiates a cell signaling cascade related causally to aberrant cell proliferation and carcinogenesis.
authors.affiliation: Department of Pathology, University of Vermont, Burlington 05405, USA. ctimblin@zoo.uvm.edu
authors.forename: C
authors.initials: C
authors.lastname: Timblin
authors.forename: K
authors.initials: K
authors.lastname: BeruBe
authors.forename: A
authors.initials: A
authors.lastname: Churg
authors.forename: K
authors.initials: K
authors.lastname: Driscoll
authors.forename: T
authors.initials: T
authors.lastname: Gordon
authors.forename: D
authors.initials: D
authors.lastname: Hemenway
authors.forename: E
authors.initials: E
authors.lastname: Walsh
authors.forename: A B
authors.initials: AB
authors.lastname: Cummins
authors.forename: P
authors.initials: P
authors.lastname: Vacek
authors.forename: B
authors.initials: B
authors.lastname: Mossman
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008168:Lung / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D051381:Rats; D018808:Transcription Factor AP-1 / Q000502:physiology
chemical_list: D018808:Transcription Factor AP-1; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D001973:Bromodeoxyuridine