{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:13:38Z","timestamp":1792502018830,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T00:00:00Z","timestamp":1625875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ratchadapisek sompotch Fund, Chulalongkorn University","award":["CU_GR_63_95_30_02"],"award-info":[{"award-number":["CU_GR_63_95_30_02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03b1 (TNF\u03b1)-stimulated fibroblast-like synoviocytes (FLS). FLS were isolated from the synovium of knee osteoarthritis (OA) patients undergoing surgery. NDMVs, isolated from TNF\u03b1-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\u201324 h time period, with no significant change in cell viability. TNF\u03b1 stimulated the cytokine expression in FLS, and NDMVs down-regulated TNF\u03b1-induced expression of IL-5, IL-6, IL-8, MCP-1, IFN\u03b3 and MIP-1\u03b2. However, this down-regulation was selective, as NDMVs had no significant effects on TNF\u03b1-stimulated expression of IL-2 or IL-4. NDMVs were internalized by FLS to inhibit TNF\u03b1-stimulated broad-spectrum proinflammatory cytokine secretion. NDMVs, therefore, may exhibit an anti-inflammatory role in the regulation of the FLS function.<\/jats:p>","DOI":"10.3390\/ijms22147409","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:23:36Z","timestamp":1626049416000},"page":"7409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Internalization of Neutrophil-Derived Microvesicles Modulates TNF\u03b1-Stimulated Proinflammatory Cytokine Production in Human Fibroblast-Like Synoviocytes"],"prefix":"10.3390","volume":"22","author":[{"given":"Dong","family":"Zhan","sequence":"first","affiliation":[{"name":"Joint PhD Program in Biomedical Sciences and Biotechnology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Human Anatomy Laboratory of Experimental Teaching Centre, School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Cross","sequence":"additional","affiliation":[{"name":"Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Department of Academic Rheumatology, Aintree University Hospital, Liverpool L9 7AL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen L.","family":"Wright","sequence":"additional","affiliation":[{"name":"Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-6211","authenticated-orcid":false,"given":"Robert J.","family":"Moots","sequence":"additional","affiliation":[{"name":"Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Department of Academic Rheumatology, Aintree University Hospital, Liverpool L9 7AL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3852-9092","authenticated-orcid":false,"given":"Sittisak","family":"Honsawek","sequence":"additional","affiliation":[{"name":"Osteoarthritis and Musculoskeleton Research Unit, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Vinai Parkpian Orthopaedic Research Centre, Department of Orthopaedics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.joca.2012.08.027","article-title":"Synovial inflammation, immune cells and their cytokines in osteoarthritis: A review","volume":"20","author":"Zuurmond","year":"2012","journal-title":"Osteoarthr. 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