Negative impact of DEP exposure on human airway epithelial cell adhesion, stiffness, and repair.
Epidemiological and experimental studies suggest that diesel exhaust particles (DEPs) may be associated with increased respiratory mortality and morbidity. Several recent studies have also shown that DEPs increase the production of inflammatory cytokines by human bronchial epithelium (HBE) cells in vitro. The present study investigates the effects of DEPs on the interaction of l-HBE cells (16HBE14o-) with the cell and matrix microenvironment based on evaluation of integrin-type cell/matrix ligand expression, cytoskeleton (CSK) stiffness, and matrix remodeling via matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 expression. The results showed that DEP exposure induced: 1) a net dose-dependent decrease in CSK stiffness through actin fibers, 2) a concomitant specific reduction of both alpha(3)- and beta(1)-integrin subunits extensively expressed on the HBE cell surface, 3) a decrease in the level of CD44, which is a major HBE cell-cell and HBE cell-matrix adhesion molecule; and 4) an isolated decrease in MMP-1 expression without any change in tissue inhibitor of matrix metalloproteinase (TIMP)-1 or TIMP-2 tissue inhibitors. Restrictive modulation of cell-matrix interaction, cell-cell connection, CSK stiffness, and fibrillary collagen remodeling results in a decreased wound closure capacity and an increased deadhesion capacity. In conclusion, on the basis of these results, we can propose that, in addition to their ability to increase the production of inflammatory cytokines, DEPs could also alter the links between actin CSK and the extracellular matrix, suggesting that they might facilitate HBE cell detachment in vivo.
Doornaert
Blandine
B
Faculté de Médecine, Faculté des Sciences Université Paris XII, Institut National de la Santé et de la Recherche Médicale, Unité 492 de Physiopathologie et Thérapeutique Respiratoire, 8 rue du Général Sarrail, 94010 Créteil Cedex, France.
Leblond
Valerie
V
Galiacy
Stephane
S
Gras
Gabriel
G
Planus
Emmanuelle
E
Laurent
Valerie
V
Isabey
Daniel
D
Lafuma
Chantal
C
D000199:Actins / Q000502:physiology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D039423:Integrin alpha1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D010587:Phagocytosis; D020033:Protein Isoforms / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000502:physiology*; D001335:Vehicle Emissions / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects*
D000199:Actins; D018960:Hyaluronan Receptors; D039423:Integrin alpha1; D019012:Integrin beta1; D020033:Protein Isoforms; D001335:Vehicle Emissions; D020781:Matrix Metalloproteinase 1