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Monosodium urate crystal induced macrophage inflammation is attenuated by chondroitin sulphate: pre-clinical model for gout prophylaxis?

dc.contributor.author Kraus, Virginia
dc.contributor.author Orlowsky, Eric W
dc.contributor.author Stabler, Thomas V
dc.contributor.author Montell, Eulàlia
dc.contributor.author Vergés, Josep
dc.date.accessioned 2019-02-02T15:32:40Z
dc.date.available 2019-02-02T15:32:40Z
dc.date.issued 2014-09-27
dc.identifier 1471-2474-15-318
dc.identifier.issn 1471-2474
dc.identifier.issn 1471-2474
dc.identifier.uri https://hdl.handle.net/10161/18053
dc.description.abstract Chondroitin Sulphate (CS), a natural glycosaminoglycan of the extracellular matrix, has clinical benefit in symptomatic osteoarthritis but has never been tested in gout. In vitro, CS has anti-inflammatory and positive effects on osteoarthritic chondrocytes, synoviocytes and subchondral bone osteoblasts, but its effect on macrophages is unknown. The purpose of our study was to evaluate the in vitro effects of CS on monosodium urate (MSU)-stimulated cytokine production by macrophages.THP-1 monocytes were differentiated into mature macrophages using a phorbol ester, pretreated for 4 hours with CS in a physiologically achievable range of concentrations (10-200 μg/ml) followed by MSU crystal stimulation for 24 hours. Cell culture media were analyzed by immunoassay for factors known to be upregulated during gouty inflammation including IL-1β, IL-8 and TNFα. The specificity of inflammasome activation by MSU crystals was tested with a caspase-1 inhibitor (0.01 μM-10 μM).MSU crystals ≥10 mg/dl increased macrophage production of IL-1β, IL-8 and TNFα a mean 7-, 3- and 4-fold respectively. Induction of IL-1β by MSU was fully inhibited by a caspase-1 inhibitor confirming inflammasome activation as the mechanism for generating this cytokine. In a dose-dependent manner, CS significantly inhibited IL-1β (p = 0.003), and TNFα (p = 0.02) production from macrophages in response to MSU. A similar trend was observed for IL-8 but was not statistically significant (p = 0.41).CS attenuated MSU crystal induced macrophage inflammation, suggesting a possible role for CS in gout prophylaxis.
dc.language eng
dc.publisher Springer Nature
dc.relation.ispartof BMC musculoskeletal disorders
dc.relation.isversionof 10.1186/1471-2474-15-318
dc.subject Monocytes
dc.subject Cell Line
dc.subject Macrophages
dc.subject Humans
dc.subject Gout
dc.subject Inflammation
dc.subject Uric Acid
dc.subject Chondroitin Sulfates
dc.subject Drug Evaluation, Preclinical
dc.subject Dose-Response Relationship, Drug
dc.title Monosodium urate crystal induced macrophage inflammation is attenuated by chondroitin sulphate: pre-clinical model for gout prophylaxis?
dc.type Journal article
dc.date.updated 2019-02-02T15:32:39Z
pubs.begin-page 318
pubs.issue 1
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Orthopaedics
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Pathology
pubs.organisational-group Medicine, Rheumatology and Immunology
pubs.organisational-group Medicine
pubs.publication-status Published
pubs.volume 15


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