Monosodium urate crystal induced macrophage inflammation is attenuated by chondroitin sulphate: pre-clinical model for gout prophylaxis?
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BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: CS attenuated MSU crystal induced macrophage inflammation, suggesting a possible role for CS in gout prophylaxis.
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Published Version (Please cite this version)10.1186/1471-2474-15-318
Publication InfoOrlowsky, EW; Stabler, TV; Montell, E; Vergés, J; & Kraus, VB (2014). Monosodium urate crystal induced macrophage inflammation is attenuated by chondroitin sulphate: pre-clinical model for gout prophylaxis?. BMC Musculoskelet Disord, 15. pp. 318. 10.1186/1471-2474-15-318. Retrieved from https://hdl.handle.net/10161/10862.
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Professor of Medicine
My special area of expertise is as a clinician scientist investigating osteoarthritis. Osteoarthritis is the most common form of joint disease in man and its incidence increases with age. It is a problem of increasing concern to the medical community due to the increasing longevity of the population. Trained as a molecular biologist and a Rheumatologist, I endeavor to study this disease from bedside to bench. The work in this laboratory focuses on osteoarthritis and deals w