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http://purl.uniprot.org/citations/24470119http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24470119http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known. We undertook this study to analyze the costimulatory properties of myeloid-related protein 8 (MRP-8) and MRP-14 (endogenous Toll-like receptor 4 [TLR-4] agonists) in MSU crystal-induced IL-1β secretion and their relevance in gout.

Methods

MRP-8/MRP-14 was measured in paired serum and synovial fluid samples by enzyme-linked immunosorbent assay (ELISA) and localized in synovial tissue from gout patients by immunohistochemistry. Serum levels were correlated with disease activity, and MSU crystal-induced release of MRPs from human phagocytes was measured. Costimulatory effects of MRP-8 and MRP-14 on MSU crystal-induced IL-1β secretion from phagocytes were analyzed in vitro by ELISA, Western blotting, and polymerase chain reaction. The impact of MRP was tested in vivo in a murine MSU crystal-induced peritonitis model.

Results

MRP-8/MRP-14 levels were elevated in the synovium, tophi, and serum of patients with gout and correlated with disease activity. MRP-8/MRP-14 was released by MSU crystal-activated phagocytes and increased MSU crystal-induced IL-1β secretion in a TLR-4-dependent manner. Targeted deletion of MRP-14 in mice led to a moderately reduced response of MSU crystal-induced inflammation in vivo.

Conclusion

MRP-8 and MRP-14, which are highly expressed in gout, are enhancers of MSU crystal-induced IL-1β secretion in vitro and in vivo. These endogenous TLR-4 ligands released by activated phagocytes contribute to the maintenance of inflammation in gout."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.org/dc/terms/identifier"doi:10.1002/art.38369"xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Roth J."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Gabay C."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Vogl T."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Bas S."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Busso N."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Holzinger D."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Foell D."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Weinhage T."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Merriman T."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Ives A."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Dalbeth N."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Pool B."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Baeten D."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Nippe N."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Mysore V."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/author"Marketon K."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/name"Arthritis Rheumatol"xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/pages"1327-1339"xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/title"Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout."xsd:string
http://purl.uniprot.org/citations/24470119http://purl.uniprot.org/core/volume"66"xsd:string
http://purl.uniprot.org/citations/24470119http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24470119
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