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Monosodium urate microcrystals induce cyclooxygenase-2 in human monocytes
M Pouliot1, M J James, S R McColl
1Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia.
Blood
|March 21, 1998
Summary
Monosodium urate (MSU) crystals trigger gouty arthritis by inducing cyclooxygenase-2 (COX-2) in monocytes. This leads to inflammatory prostaglandin and thromboxane synthesis, implicating COX-2 in gout development.
Area of Science:
- Immunology
- Biochemistry
- Rheumatology
Background:
- Gouty arthritis is an inflammatory condition caused by monosodium urate (MSU) crystal deposition.
- Mononuclear phagocyte activation is a key early event in gout attacks.
- Stimulated mononuclear phagocytes are a significant source of inducible cyclooxygenase-2 (COX-2).
Purpose of the Study:
- To investigate the effect of proinflammatory microcrystals on COX-2 protein expression in crystal-stimulated monocytes.
- To determine the role of COX-2 in MSU-induced inflammation.
Main Methods:
- Monocytes were stimulated with MSU and calcium pyrophosphate dihydrate (CPPD) crystals.
- COX-2 protein expression, prostaglandin E2 (PGE2), and thromboxane A2 (TXA2) synthesis were measured.
- Inhibitors of tyrosine phosphorylation (herbimycin A), p38 MAPK (SB 203580), and colchicine were used to assess pathway involvement.
Main Results:
- MSU crystals, but not CPPD crystals, induced COX-2 expression and prostanoid synthesis (PGE2, TXA2).
- Crystal-induced COX-2 synthesis involved transcriptional and translational events.
- Inhibition of tyrosine phosphorylation, p38 MAPK, and colchicine treatment blocked MSU-induced COX-2 and prostanoid synthesis.
Conclusions:
- MSU crystals induce COX-2 expression in monocytes, contributing to gouty arthritis pathogenesis.
- COX-2 plays a critical role in the inflammatory response to MSU crystals.
- Targeting COX-2 may be a therapeutic strategy for managing gouty arthritis.