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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/L170    most recent 00445.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Amara, N. Articles by Boczkowski, J. Search for Related Content PubMed PubMed Citation Articles by Amara, N. Articles by Boczkowski, J.

Diesel exhaust particles induce matrix metalloprotease-1 in human lung epithelial cells via a NADP(H) oxidase/NOX4 redox-dependent mechanism

¹Institut National de la Santé et de la Recherche Médicale (INSERM) U700 and ²INSERM U773 and Centre de Recherche Bichat Beaujon CRB3, Paris, France; Université Paris 7 Denis Diderot, Faculté de Médecine, site Bichat, Paris, France; ³Faculté des Sciences de Gabès, Tunisia; ⁴Department of Medical Biotechnology, Jagiellonian University, Krakow, Poland; ⁵Department of Pathology, Immunology and Clinical Pathology, Centre Medical Universitaire, Geneva, Switzerland; and ⁶Assistance Publique Hopitaux de Paris, CIC 007, Hôpital Bichat, Paris, France

Submitted 10 November 2006 ; accepted in final form 17 April 2007

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.

chronic obstructive pulmonary disease; environment; pollution; nanoparticles