PMID- 28223796 OWN - NLM STAT- MEDLINE DCOM- 20170417 LR - 20220423 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 12 DP - 2017 TI - Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes. PG - 1019-1031 LID - 10.2147/IJN.S123484 [doi] AB - 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 microg/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. FAU - Vandivort, Tyler C AU - Vandivort TC AD - Cedars-Sinai Medical Center, Women's Guild Lung Institute, Los Angeles, CA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA. FAU - Birkland, Timothy P AU - Birkland TP AD - Cedars-Sinai Medical Center, Women's Guild Lung Institute, Los Angeles, CA. FAU - Domiciano, Talita P AU - Domiciano TP AD - Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA. FAU - Mitra, Somenath AU - Mitra S AD - Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, USA. FAU - Kavanagh, Terrance J AU - Kavanagh TJ AD - Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA. FAU - Parks, William C AU - Parks WC AD - Cedars-Sinai Medical Center, Women's Guild Lung Institute, Los Angeles, CA. LA - eng GR - R01 HL141078/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20170207 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Inflammation Mediators) RN - 0 (Nanotubes, Carbon) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.24.22 (Matrix Metalloproteinase 10) SB - IM MH - Animals MH - Bronchoalveolar Lavage MH - Caspase 3/metabolism MH - Cell Death/drug effects MH - Cytoprotection/drug effects MH - Endocytosis/drug effects MH - Inflammation/*enzymology MH - Inflammation Mediators/metabolism MH - Lung/drug effects/*enzymology/*pathology MH - Macrophages, Alveolar/drug effects/metabolism/pathology MH - Matrix Metalloproteinase 10/*metabolism MH - Mice, Inbred C57BL MH - Nanotubes, Carbon/*toxicity MH - Pneumonia/pathology PMC - PMC5304974 OTO - NOTNLM OT - MMP-10 OT - apoptosis OT - lung injury OT - macrophages OT - multiwalled carbon nanotubes COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2017/02/23 06:00 MHDA- 2017/04/18 06:00 PMCR- 2017/02/07 CRDT- 2017/02/23 06:00 PHST- 2017/02/23 06:00 [entrez] PHST- 2017/02/23 06:00 [pubmed] PHST- 2017/04/18 06:00 [medline] PHST- 2017/02/07 00:00 [pmc-release] AID - ijn-12-1019 [pii] AID - 10.2147/IJN.S123484 [doi] PST - epublish SO - Int J Nanomedicine. 2017 Feb 7;12:1019-1031. doi: 10.2147/IJN.S123484. eCollection 2017.