Abstract
Silver nanoparticles (AgNPs) are commonly used in commercial and medical applications. However, AgNPs may induce toxicity, extracellular matrix (ECM) changes and inflammatory responses. Fibroblasts are key players in remodeling processes and major producers of the ECM. The aims of this study were to explore the effect of AgNPs on cell viability, both ex vivo in murine precision cut lung slices (PCLS) and in vitro in human lung fibroblasts (HFL-1), and immunomodulatory responses in fibroblasts. PCLS and HFL-1 were exposed to AgNPs with different sizes, 10 nm and 75 nm, at concentrations 2 µg/mL and 10 μg/mL. Changes in synthesis of ECM proteins, growth factors and cytokines were analyzed in HFL-1. Ag10 and Ag75 affected cell viability, with significantly reduced metabolic activities at 10 μg/mL in both PCLS and HFL-1 after 48 h. AgNPs significantly increased procollagen I synthesis and release of IL-8, prostaglandin E2, RANTES and eotaxin, whereas reduced IL-6 release was observed in HFL-1 after 72 h. Our data indicate toxic effects of AgNP exposure on cell viability ex vivo and in vitro with altered procollagen and proinflammatory cytokine secretion in fibroblasts over time. Hence, careful characterizations of AgNPs are of importance, and future studies should include timepoints beyond 24 h.
Highlights
Silver nanoparticles (AgNPs) are widely used in commercial and medical applications, such as in products for disinfectants, water purification and band aids to improve wound healing, due to their antibacterial properties and characteristic features [1]
Fibroblasts are mesenchymal cells, crucial for maintaining homeostasis of extracellular matrix (ECM) proteins, such as collagens and proteoglycans, components that together act as important reservoirs for cytokines and growth factors [8,9]
There was a strong tendency (p = 0.055) that 10 μg/mL of Ag75 reduced viability in precision cut lung slices (PCLS) already after 24 h, whereas a significant decrease in metabolic activity was observed after 48 h (p < 0.0001; Figure 1B)
Summary
Silver nanoparticles (AgNPs) are widely used in commercial and medical applications, such as in products for disinfectants, water purification and band aids to improve wound healing, due to their antibacterial properties and characteristic features [1]. In a previous in vitro study, long-term exposure of lung epithelial cells to AgNPs induced cytotoxicity, epithelial–mesenchymal transition (EMT) and increased collagen deposition [6,7], implicating a pro-fibrotic response by the AgNPs. Upon damages of the airway epithelial cell layer due to chronic lung disease or chronic exposure of inhaled particles, cells beneath the epithelial basement membrane will become exposed to nanoparticles, triggering an inflammatory response that may promote locally enhanced levels of pro-inflammatory cytokines. In the present study, which is partly a follow up study to Gliga et al, [6,7], we have used AgNPs with different sizes (10 nm and 75 nm) and concentrations (2 μg/mL and 10 μg/mL) up to 72 h to study potential changes on cell viability, ECM synthesis and cytokine profile in human lung fibroblasts and in murine lung tissue slices ex vivo. AgNPs were shown to have dose-dependent effects on cell viability observed both in vitro and ex vivo over time, findings that may be of relevance for future biomedical applications
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