Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes

Tyler C Vandivort,1,2 Timothy P Birkland,1 Talita P Domiciano,3 Somenath Mitra,4 Terrance J Kavanagh,2 William C Parks1 1Cedars-Sinai Medical Center, Women’s Guild Lung Institute, Los Angeles, CA, 2Department of Environmental and Occupational Health Sciences, University of Washington, Sea...

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Autores principales:	Vandivort TC, Birkland TP, Domiciano TP, Mitra S, Kavanagh TJ, Parks WC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	MMP-10 Multi-walled carbon nanotubes lung injury macrophages apoptosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7bb4ca083eaa4f87b832d1e43a98d1fb
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spelling	oai:doaj.org-article:7bb4ca083eaa4f87b832d1e43a98d1fb2021-12-02T02:42:27ZStromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes1178-2013https://doaj.org/article/7bb4ca083eaa4f87b832d1e43a98d1fb2017-02-01T00:00:00Zhttps://www.dovepress.com/stromelysin-2-mmp-10-facilitates-clearance-and-moderates-inflammation--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tyler C Vandivort,1,2 Timothy P Birkland,1 Talita P Domiciano,3 Somenath Mitra,4 Terrance J Kavanagh,2 William C Parks1 1Cedars-Sinai Medical Center, Women’s Guild Lung Institute, Los Angeles, CA, 2Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 3Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA, 4Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, USA Abstract: Multiwalled carbon nanotubes (MWCNTs) are nanomaterials composed of multiple layers of graphene cylinders with unique properties that make them valuable for a number of industries. However, rising global production has led to concerns regarding potential occupational exposures to them as raw materials during handling. This is especially true for long MWCNT fibers, whose aspect ratio has been posited to initiate pathology similar to that of asbestos. Matrix metalloproteinases (MMPs) are a class of extracellular endopeptidases that control various processes related to tissue repair, inflammation, and more. Stromelysin-2 (MMP-10) has roles in modulating macrophage activation and function, and hence, we used an MMP-10 null (Mmp10-/-) mouse model to assess its role in controlling lung responses to inhaled long MWCNTs. Oropharyngeal aspiration of long MWCNTs (80 µg/mouse) by wild-type mice induced expression of Mmp10 mRNA, which was accompanied by a robust inflammatory response characterized by elevated expression of Tnfa, Il6, and Il1b. In Mmp10-/- mice, we found that absence of MMP-10 led to impaired pulmonary clearance of MWCNTs and reduced macrophage cell survival. Exposure of wild-type bone marrow-derived macrophages (BMDMs) and alveolar macrophages to MWCNTs caused a rapid, dose-dependent upregulation of Mmp10 mRNA expression, which was accompanied by expression of pro-inflammatory products (Il6 and Il1b). These products were further enhanced in Mmp10-/- macrophages, resulting in increased caspase-3-dependent cell death compared with wild-type cells. These findings indicate that MMP-10 facilitates the clearance of MWCNTs and moderates the pro-inflammatory response of exposed alveolar and infiltrated macrophages. Keywords: MMP-10, multiwalled carbon nanotubes, lung injury, macrophages, apoptosisVandivort TCBirkland TPDomiciano TPMitra SKavanagh TJParks WCDove Medical PressarticleMMP-10Multi-walled carbon nanotubeslung injurymacrophagesapoptosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1019-1031 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	MMP-10 Multi-walled carbon nanotubes lung injury macrophages apoptosis Medicine (General) R5-920
spellingShingle	MMP-10 Multi-walled carbon nanotubes lung injury macrophages apoptosis Medicine (General) R5-920 Vandivort TC Birkland TP Domiciano TP Mitra S Kavanagh TJ Parks WC Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes
description	Tyler C Vandivort,1,2 Timothy P Birkland,1 Talita P Domiciano,3 Somenath Mitra,4 Terrance J Kavanagh,2 William C Parks1 1Cedars-Sinai Medical Center, Women’s Guild Lung Institute, Los Angeles, CA, 2Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 3Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA, 4Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, USA Abstract: Multiwalled carbon nanotubes (MWCNTs) are nanomaterials composed of multiple layers of graphene cylinders with unique properties that make them valuable for a number of industries. However, rising global production has led to concerns regarding potential occupational exposures to them as raw materials during handling. This is especially true for long MWCNT fibers, whose aspect ratio has been posited to initiate pathology similar to that of asbestos. Matrix metalloproteinases (MMPs) are a class of extracellular endopeptidases that control various processes related to tissue repair, inflammation, and more. Stromelysin-2 (MMP-10) has roles in modulating macrophage activation and function, and hence, we used an MMP-10 null (Mmp10-/-) mouse model to assess its role in controlling lung responses to inhaled long MWCNTs. Oropharyngeal aspiration of long MWCNTs (80 µg/mouse) by wild-type mice induced expression of Mmp10 mRNA, which was accompanied by a robust inflammatory response characterized by elevated expression of Tnfa, Il6, and Il1b. In Mmp10-/- mice, we found that absence of MMP-10 led to impaired pulmonary clearance of MWCNTs and reduced macrophage cell survival. Exposure of wild-type bone marrow-derived macrophages (BMDMs) and alveolar macrophages to MWCNTs caused a rapid, dose-dependent upregulation of Mmp10 mRNA expression, which was accompanied by expression of pro-inflammatory products (Il6 and Il1b). These products were further enhanced in Mmp10-/- macrophages, resulting in increased caspase-3-dependent cell death compared with wild-type cells. These findings indicate that MMP-10 facilitates the clearance of MWCNTs and moderates the pro-inflammatory response of exposed alveolar and infiltrated macrophages. Keywords: MMP-10, multiwalled carbon nanotubes, lung injury, macrophages, apoptosis
format	article
author	Vandivort TC Birkland TP Domiciano TP Mitra S Kavanagh TJ Parks WC
author_facet	Vandivort TC Birkland TP Domiciano TP Mitra S Kavanagh TJ Parks WC
author_sort	Vandivort TC
title	Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes
title_short	Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes
title_full	Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes
title_fullStr	Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes
title_full_unstemmed	Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes
title_sort	stromelysin-2 (mmp-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/7bb4ca083eaa4f87b832d1e43a98d1fb
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Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes

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