{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:11:57Z","timestamp":1770819117625,"version":"3.50.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR067748"],"award-info":[{"award-number":["R01AR067748"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1\u03b2 secretion \u00b1 recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Acute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry. PBMCs were primed with Pam3CSK4 (1\u03bcg\/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU (200\u03bcg\/mL) stimulated IL-1\u03b2 secretion was determined by ELISA. Reactive oxygen species (ROS) generation in monocytes was determined fluorometrically. PBMCs were incubated with IL-1RA (250ng\/mL) or rhPRG4 (200\u03bcg\/mL) and bead phagocytosis by monocytes was determined. THP-1 monocytes were treated with MSU crystals \u00b1 rhPRG4 and cellular levels of NLRP3 protein, pro-IL-1\u03b2, secreted IL-1\u03b2, and activities of caspase-1 and protein phosphatase-2A (PP2A) were quantified. The peritoneal influx of inflammatory and anti-inflammatory monocytes and neutrophils in Prg4 deficient mice was studied and the impact of rhPRG4 on immune cell trafficking was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Enhanced phagocytic activation of gout monocytes under basal conditions (<jats:italic>p&amp;lt;0.001<\/jats:italic>) was associated with ROS generation and MSU stimulated IL-1\u03b2 secretion (<jats:italic>p&amp;lt;0.05<\/jats:italic>). rhPRG4 reduced bead phagocytosis by normal and gout monocytes compared to IL-1RA and both treatments were efficacious in reducing IL-1\u03b2 secretion (<jats:italic>p&amp;lt;0.05<\/jats:italic>). rhPRG4 reduced pro-IL-1\u03b2 content, caspase-1 activity, conversion of pro-IL-1\u03b2 to mature IL-1\u03b2 and restored PP2A activity in monocytes (<jats:italic>p&amp;lt;0.05<\/jats:italic>). PP2A inhibition reversed rhPRG4\u2019s effects on pro-IL-1\u03b2 and mature IL-1\u03b2 in MSU stimulated monocytes. Neutrophils accumulated in peritoneal cavities of Prg4 deficient mice (<jats:italic>p&amp;lt;0.01<\/jats:italic>) and rhPRG4 treatment reduced neutrophil accumulation and enhanced anti-inflammatory monocyte influx (<jats:italic>p&amp;lt;0.05<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MSU phagocytosis was higher in gout monocytes resulting in higher ROS and IL-1\u03b2 secretion. rhPRG4 reduced monocyte phagocytic activation to a greater extent than IL-1RA and reduced IL-1\u03b2 secretion. The anti-inflammatory activity of rhPRG4 in monocytes is partially mediated by PP2A, and <jats:italic>in vivo<\/jats:italic>, PRG4 plays a role in regulating the trafficking of immune cells into the site of a gout flare.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.771677","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T11:43:59Z","timestamp":1640087039000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation of Monocytes and Reduces IL-1\u03b2 Secretion by Urate Crystal Stimulated Gout PBMCs"],"prefix":"10.3389","volume":"12","author":[{"given":"Sandy","family":"ElSayed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory 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