title: Titanium dioxide nanoparticles induce matrix metalloprotease 1 in human pulmonary fibroblasts partly via an interleukin-1β-dependent mechanism.
abstract: Exposure to titanium dioxide (TiO2) nanoparticles (NPs) is associated with lung remodeling, but the underlying mechanisms are unknown. Matrix metalloprotease (MMP)-1 is an important actor in matrix homeostasis and could therefore participate in TiO2 NP effects. Our aim was to evaluate the effects of TiO2 NPs on MMP-1 expression and activity in lung pulmonary fibroblasts and to understand the underlying mechanisms and assess the importance of the physicochemical characteristics of the particles in these effects. Human pulmonary fibroblasts (MRC-5 cell line and primary cells) were exposed to 10 or 100 μg/cm(2) TiO2 (two anatases, two anatase/rutile mix, one rutile NP, and one micrometric) and carbon black (CB) NPs for 6 to 48 hours. We examined cell viability, MMP-1 expression and activity, and the implication of oxidative stress, transforming growth factor (TGF)-β, extracellular MMP inducer, and IL-1β in MMP-1 expression. All TiO2 NPs induced MMP-1 (mRNA and protein expression), repression of procollagen-1, and α-actin expression, but only the two anatase/rutile mix induced MMP-1 activity. Micrometric TiO2 had smaller effects than TiO2 NPs, and CB NPs did not induce MMP-1. MMP-1 induction by TiO2 NPs was not related to TGF-β, oxidative stress, or EMPRIN expression but was related to IL-1β expression, which partly drives MMP-1 induction by two TiO2 NPs (one anatase/rutile mix and the rutile one). Taken together, our results show that TiO2 NPs are potent inducers and regulators of MMP-1 expression and activity, partly via an IL-1β-dependent mechanism. This may explain TiO2 lung remodeling effects.
authors.affiliation: Unité Inserm 955, Equipe 4, Faculté de Médecine de Créteil, 8, rue du Général Sarrail, 94000 Créteil, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Armand
authors.forename: Maylis
authors.initials: M
authors.lastname: Dagouassat
authors.forename: Esther
authors.initials: E
authors.lastname: Belade
authors.forename: Angélique
authors.initials: A
authors.lastname: Simon-Deckers
authors.forename: Sabine
authors.initials: S
authors.lastname: Le Gouvello
authors.forename: Chantal
authors.initials: C
authors.lastname: Tharabat
authors.forename: Corinne
authors.initials: C
authors.lastname: Duprez
authors.forename: Pascal
authors.initials: P
authors.lastname: Andujar
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pairon
authors.forename: Jorge
authors.initials: J
authors.lastname: Boczkowski
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanone
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D051926:Basigin / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D053768:Metal Nanoparticles / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D053260:Soot / Q000494:pharmacology; D014025:Titanium / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C497886:BSG protein, human; D053583:Interleukin-1beta; D011347:Procollagen; D053260:Soot; D016212:Transforming Growth Factor beta; D051926:Basigin; C009495:titanium dioxide; D014025:Titanium; D020781:Matrix Metalloproteinase 1