Internalization of Neutrophil-Derived Microvesicles Modulates TNFα-Stimulated Proinflammatory Cytokine Production in Human Fibroblast-Like Synoviocytes



Zhan, Dong, Cross, Andrew, Wright, Helen L ORCID: 0000-0003-0442-3134, Moots, Robert J ORCID: 0000-0001-7019-6211, Edwards, Steven W ORCID: 0000-0002-7074-0552 and Honsawek, Sittisak
(2021) Internalization of Neutrophil-Derived Microvesicles Modulates TNFα-Stimulated Proinflammatory Cytokine Production in Human Fibroblast-Like Synoviocytes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (14). 7409-.

[img] Text
Final revision-ijms-1268269.docx - Author Accepted Manuscript

Download (3MB)

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.

Item Type: Article
Uncontrolled Keywords: fibroblast-like synoviocytes, neutrophil-derived microvesicles, cytokines, synovitis, osteoarthritis
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 08 Jul 2021 10:55
Last Modified: 17 Oct 2023 14:23
DOI: 10.3390/ijms22147409
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3129283