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Title: | Combustion-derived particles inhibit in vitro human lung fibroblast-mediated matrix remodeling | Authors: | BOVE, Hannelore DEVOGHT, Jens RASKING, Leen PETERS, Martijn SLENDERS, Eli Roeffaers, Maarten Jorge-Penas, Alvaro Van Oosterwyck, Hans AMELOOT, Marcel |
Issue Date: | 2018 | Publisher: | BMC | Source: | JOURNAL OF NANOBIOTECHNOLOGY, 16 (Art N° 82) | Abstract: | Background The continuously growing human exposure to combustion-derived particles (CDPs) drives in depth investigation of the involved complex toxicological mechanisms of those particles. The current study evaluated the hypothesis that CDPs could affect cell-induced remodeling of the extracellular matrix due to their underlying toxicological mechanisms. The effects of two ultrafine and one fine form of CDPs on human lung fibroblasts (MRC-5 cell line) were investigated, both in 2D cell culture and in 3D collagen type I hydrogels. A multi-parametric analysis was employed.ResultsIn vitro dynamic 3D analysis of collagen matrices showed that matrix displacement fields induced by human lung fibroblasts are disturbed when exposed to carbonaceous particles, resulting in inhibition of matrix remodeling. In depth analysis using general toxicological assays revealed that a plausible explanation comprises a cascade of numerous detrimental effects evoked by the carbon particles, including oxidative stress, mitochondrial damage and energy storage depletion. Also, ultrafine particles revealed stronger toxicological and inhibitory effects compared to their larger counterparts. The inhibitory effects can be almost fully restored when treating the impaired cells with antioxidants like vitamin C.ConclusionsThe unraveled in vitro pathway, by which ultrafine particles alter the fibroblasts' vital role of matrix remodeling, extends our knowledge about the contribution of these biologically active particles in impaired lung tissue repair mechanisms, and development and exacerbation of chronic lung diseases. The new insights may even pave the way to precautionary actions. The results provide justification for toxicological assessments to include mechanism-linked assays besides the traditional in vitro toxicological screening assays. | Notes: | [Bove, Hannelore; Devoght, Jens; Rasking, Leentje; Slenders, Eli; Ameloot, Marcel] Hasselt Univ, Biomed Res Inst, Agoralaan Bldg C, Diepenbeek, Belgium. [Bove, Hannelore; Roeffaers, Maarten] Katholieke Univ Leuven, Ctr Surface Chem & Catalysis, Celestijnenlaan 200F, Louvain, Belgium. [Peters, Martijn] Hasselt Univ, Inst Mat Res, Agoralaan Bldg D, Diepenbeek, Belgium. [Jorge-Penas, Alvaro; Van Oosterwyck, Hans] Katholieke Univ Leuven, Dept Mech Engn, Celestijnenlaan 300C,Box 2419, Louvain, Belgium. [Van Oosterwyck, Hans] Katholieke Univ Leuven, Div Skeletal Tissue Engn, Prometheus, Louvain, Belgium. | Keywords: | Combustion-derived particles; In vitro toxicology; Human lung fbroblasts; Hazard assessment; Matrix remodeling inhibition;Combustion-derived particles; In vitro toxicology; Human lung fibroblasts; Hazard assessment; Matrix remodeling inhibition | Document URI: | http://hdl.handle.net/1942/27857 | e-ISSN: | 1477-3155 | DOI: | 10.1186/s12951-018-0410-x | ISI #: | 000448504400001 | Rights: | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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bove 1.pdf | Published version | 1.56 MB | Adobe PDF | View/Open |
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