The role of miR-21 in nickel nanoparticle-induced MMP-2 and MMP-9 production in mouse primary monocytes: In vitro and in vivo studies. (December 2020)

• Record Type: Journal Article
• Authors: Mo, Yiqun; Zhang, Yue; Mo, Luke; Wan, Rong; Jiang, Mizu; Zhang, Qunwei
• Is Part Of: Environmental pollution. Volume 267(2020)
• Publication Date: 2020-12
• Subjects: Nickel nanoparticles (Nano-Ni) -- miR-21 -- Monocytes -- MMP-2 -- MMP-9; Nano-Ni Nickel nanoparticles -- Nano-Ni-P Partially passivated nickel nanoparticles -- Nano-Ni-C Carbon-coated nickel nanoparticles -- WT Wild-type -- KO Knock-out -- miR-21 microRNA-21 -- MMP-2 Matrix metalloproteinase-2 -- MMP-9 Matrix metalloproteinase-9 -- TIMP-1 Tissue inhibitor of metalloproteinase-1 -- TIMP-2 Tissue inhibitor of metalloproteinase-2 -- ECM Extracellular matrix -- RECK Reversion-inducing cysteine-rich protein with Kazal motifs -- IL-1β Interleukin 1 beta -- IL-6 Interleukin 6 -- IL-10 Interleukin 10 -- TNFα Tumor necrosis factor alpha -- TGF-β1 Transforming growth factor beta 1 -- HIF-1α Hypoxia inducible factor 1α -- DAPI 4′, 6-diamidino-2-phenylindole -- ROS Reactive oxygen species; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2020.115597
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Exposure to metal nanoparticles causes both pulmonary and systemic effects. Nanoparticles can enter the circulation and act directly or indirectly on blood cells, such as monocytes. Monocytes/macrophages are among the first cells to home to inflammatory sites and play a key role in the immune response. Here we investigated the effects of nickel nanoparticles (Nano-Ni), partially [O]-passivated Nano-Ni (Nano-Ni-P), and carbon-coated Nano-Ni (Nano-Ni-C) on MMP-2 and MMP-9 production in mouse primary monocytes both in vitro and in vivo and explored the potential mechanisms involved. The dose- and time-response studies showed that exposure of primary monocytes from wild-type (WT) mice to 30 μg/mL of Nano-Ni for 24 h caused significant MMP-2 and MMP-9 production; therefore, these dose and time point were chosen for the following in vitro studies. Nano-Ni and Nano-Ni-P caused miR-21 upregulation, as well as MMP-2, MMP-9, TIMP-1 and TIMP-2 upregulation in monocytes from WT, but not miR-21 knock-out (KO), mice, indicating the important role of miR-21 in Nano-Ni-induced MMPs and TIMPs upregulation. However, Nano-Ni-C did not cause these effects, suggesting surface modification of Nano-Ni, such as carbon coating, alleviates Nano-Ni-induced miR-21 and MMPs upregulation. These results were further confirmed by in vivo studies by intratracheal instillation of nickel nanoparticles into WT and miR-21 KO mice. Finally, our results demonstrated that exposure of primary monocytes from WT mice to Nano-Ni and Nano-Ni-P caused downregulation of RECK, a direct miR-21 target, suggesting the involvement of miR-21/RECK pathway in Nano-Ni-induced MMP-2 and MMP-9 production. Graphical abstract: Image 1 Highlights: Primary monocytes were isolated from mouse peripheral blood. Nano-Ni upregulated miR-21, MMP-2 and MMP-9, and downregulated RECK in WT monocytes. Nano-Ni did not cause the above effects in monocytes from miR-21 knock-out mice. Carbon-coating (Nano-Ni-C) ameliorated Nano-Ni-induced MMP-2/9 upregulation. miR-21/RECK pathway is involved in Nano-Ni-induced MMP-2/9 production.