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http://purl.uniprot.org/citations/34992596 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/34992596 | http://www.w3.org/2000/01/rdf-schema#comment | "ObjectivesTo 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-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.MethodsAcute 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 (1μg/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU (200μg/mL) stimulated IL-1β 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 (200μg/mL) and bead phagocytosis by monocytes was determined. THP-1 monocytes were treated with MSU crystals ± rhPRG4 and cellular levels of NLRP3 protein, pro-IL-1β, secreted IL-1β, 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.ResultsEnhanced phagocytic activation of gout monocytes under basal conditions (p<0.001) was associated with ROS generation and MSU stimulated IL-1β secretion (p<0.05). rhPRG4 reduced bead phagocytosis by normal and gout monocytes compared to IL-1RA and both treatments were efficacious in reducing IL-1β secretion (p<0.05). rhPRG4 reduced pro-IL-1β content, caspase-1 activity, conversion of pro-IL-1β to mature IL-1β and restored PP2A activity in monocytes (p<0.05). PP2A inhibition reversed rhPRG4's effects on pro-IL-1β and mature IL-1β in MSU stimulated monocytes. Neutrophils accumulated in peritoneal cavities of Prg4 deficient mice (p<0.01) and rhPRG4 treatment reduced neutrophil accumulation and enhanced anti-inflammatory monocyte influx (p<0.05).ConclusionsMSU phagocytosis was higher in gout monocytes resulting in higher ROS and IL-1β secretion. rhPRG4 reduced monocyte phagocytic activation to a greater extent than IL-1RA and reduced IL-1β secretion. The anti-inflammatory activity of rhPRG4 in monocytes is partially mediated by PP2A, and in vivo, PRG4 plays a role in regulating the trafficking of immune cells into the site of a gout flare."xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.org/dc/terms/identifier | "doi:10.3389/fimmu.2021.771677"xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/author | "Jay G.D."xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/author | "Schmidt T.A."xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/author | "Qadri M."xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/author | "Cabezas R."xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/author | "Elsaid K.A."xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/author | "ElSayed S."xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/name | "Front Immunol"xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/pages | "771677"xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/title | "Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation of Monocytes and Reduces IL-1beta Secretion by Urate Crystal Stimulated Gout PBMCs."xsd:string |
http://purl.uniprot.org/citations/34992596 | http://purl.uniprot.org/core/volume | "12"xsd:string |
http://purl.uniprot.org/citations/34992596 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34992596 |
http://purl.uniprot.org/citations/34992596 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34992596 |
http://purl.uniprot.org/uniprot/#_B7Z4R8-mappedCitation-34992596 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34992596 |
http://purl.uniprot.org/uniprot/#_B4DW29-mappedCitation-34992596 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34992596 |
http://purl.uniprot.org/uniprot/#_B7Z759-mappedCitation-34992596 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34992596 |
http://purl.uniprot.org/uniprot/#_B3KQ20-mappedCitation-34992596 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34992596 |
http://purl.uniprot.org/uniprot/#_Q92954-mappedCitation-34992596 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34992596 |
http://purl.uniprot.org/uniprot/Q92954 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34992596 |
http://purl.uniprot.org/uniprot/B7Z759 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34992596 |
http://purl.uniprot.org/uniprot/B7Z4R8 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34992596 |
http://purl.uniprot.org/uniprot/B4DW29 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34992596 |