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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Diesel exhaust particles induce matrix metalloprotease-1 in human lung epithelial cells via a NADP(H) oxidase/NOX4 redox-dependent mechanism
American Journal of Physiology - Lung Cellular and Molecular Physiology, Volume 293, No. 1, Year 2007
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Description
Chronic exposure to particulate air pollution is associated with lung function impairment. To determine the molecular mechanism(s) of this phenomenon, we investigated, in an alveolar human epithelial cell line (A549), whether diesel exhaust particles (DEPs), a main component of particulate air pollution, modulates the expression and activity of the matrix metalloprotease (MMP)-1, a collagenase involved in alveolar wall degradation. Interaction of DEPs with cigarette smoke, which also produces structural and functional lung alterations, was also investigated. A noncytotoxic concentration of DEPs induced an increase in MMP-1 mRNA and protein expression and activity in A549 cells without modifying the expression of the MMP inhibitors TIMP-1 and -2. This effect was not potentiated when cells were coexposed to noncytotoxic concentrations of cigarette smoke condensate. DEP-induced MMP-1 was associated with increased ERK 1/2 phosphorylation and upregulation of expression and activity of the NADPH oxidase analog NOX4. Cell transfection with a NOX4 small interfering RNA prevented these phenomena, showing the critical role of a NOX4 ERK 1/2 pathway in DEP-induced MMP-1 expression and activity. Similar results to those observed in A549 cells were obtained in another human lung epithelial cell line, NCI-H292. Furthermore, experiments in mice intratracheally instilled with DEPs confirmed the in vitro findings, showing the induction of NOX4 and MMP-1 protein expression in alveolar epithelial cells. We conclude that alveolar alterations secondary to MMP-1 induction could explain lung function impairment associated with exposure to particulate pollution. Copyright © 2007 the American Physiological Society.
Authors & Co-Authors
Amara, Nadia
France, Paris
Inserm
Bachoual, Rafik
France, Paris
Inserm
Tunisia, Gabes
Université de Gabès
Desmard, Mathieu
France, Paris
Inserm
Gołda, Sławomir
France, Paris
Inserm
Poland, Krakow
Uniwersytet Jagielloński
Guichard, Cécile
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Switzerland, Geneva
Université de Genève Faculté de Médecine
Lanone, Sophie
France, Paris
Inserm
Aubier, Michel A.
France, Paris
Inserm
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Ogier-Denis, Éric
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Boczkowski, Jorge
France, Paris
Inserm
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Statistics
Citations: 90
Authors: 9
Affiliations: 7
Identifiers
Doi:
10.1152/ajplung.00445.2006
ISSN:
10400605
e-ISSN:
15221504
Research Areas
Environmental
Substance Abuse