Abstract
Neutrophil-derived microvesicles (NDMVs) have the potential to exert anti-inflammatory effects. Our study aimed to explore the effects of NDMVs on proinflammatory cytokines expressed by tumor necrosis factor α (TNFα)-stimulated fibroblast-like synoviocytes (FLS). FLS were isolated from the synovium of knee osteoarthritis (OA) patients undergoing surgery. NDMVs, isolated from TNFα-stimulated healthy neutrophils, were characterized by electron microscopy and nanoparticle tracking analysis. MTT and scratch wound healing assays were used to measure FLS viability and migration after treatment with NDMVs, while internalization of fluorescently labeled NDMVs was appraised by flow cytometry and confocal microscopy. Levels of proinflammatory cytokines in supernatants were quantified by the Bio-Plex system. Incubation of FLS with NDMVs at a vesicle/cell ratio of 100 resulted in a time-dependent uptake, with 35% of synoviocytes containing microvesicles over a 6–24 h time period, with no significant change in cell viability. TNFα stimulated the cytokine expression in FLS, and NDMVs down-regulated TNFα-induced expression of IL-5, IL-6, IL-8, MCP-1, IFNγ and MIP-1β. However, this down-regulation was selective, as NDMVs had no significant effects on TNFα-stimulated expression of IL-2 or IL-4. NDMVs were internalized by FLS to inhibit TNFα-stimulated broad-spectrum proinflammatory cytokine secretion. NDMVs, therefore, may exhibit an anti-inflammatory role in the regulation of the FLS function.
Highlights
Osteoarthritis (OA) is a degenerative disease of synovial joints resulting from cartilage loss that manifests as articular pain and osteophytes
Nanoparticle tracking analysis (NTA), which measures the Brownian motion of Neutrophil-derived microvesicles (NDMVs) (Figure 1C), illustrated that the diameter ranged from 38.4 to 1000.0 nm, with a mean value of 232.3 ± 8.9 nm
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Summary
Osteoarthritis (OA) is a degenerative disease of synovial joints resulting from cartilage loss that manifests as articular pain and osteophytes. Fibroblast-like synoviocytes (FLS) are the main cellular type in the intima layer of the synovium and they regulate homeostasis and tissue repair within the synovial joint. There are three major types of EVs: exosomes, microvesicles (MVs) and apoptotic bodies, which are characterized by their size and composition. NDMVs have been delineated to block the polarization of monocytederived macrophages to indirectly influence the activation of FLS [10]. In addition to their anti-inflammatory properties, NDMVs can regulate chondrocyte function by decreasing IL-8 and prostaglandin E2 release, and by increasing extracellular matrix components to maintain cartilage function [11]
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