Monosodium urate crystal induced macrophage inflammation is attenuated by chondroitin sulphate: pre-clinical model for gout prophylaxis?
Abstract
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.
Type
Journal articleSubject
Cell LineChondroitin Sulfates
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Gout
Humans
Inflammation
Macrophages
Monocytes
Uric Acid
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https://hdl.handle.net/10161/10862Published Version (Please cite this version)
10.1186/1471-2474-15-318Publication Info
Orlowsky, 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Virginia Byers Kraus
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

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