Pouliot M, James M J, McColl S R, Naccache P H, Cleland L G
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia.
Blood. 1998 Mar 1;91(5):1769-76.
The formation and deposition of monosodium urate (MSU) microcrystals in articular and periarticular tissues is the causative agent of acute or chronic inflammatory responses known as gouty arthritis. Mononuclear phagocyte activation is involved in early triggering events of gout attacks. Because stimulated mononuclear phagocytes can constitute an important source of the inducible isoform of cyclooxygenase (COX-2), we evaluated the effects that proinflammatory microcrystals might have on COX-2 protein expression in crystal-stimulated monocytes. We found that MSU crystals, but not calcium pyrophosphate dihydrate (CPPD) crystals, induced COX-2, which correlated with the synthesis of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2). Crystal-induced de novo synthesis of COX-2 was dependent on transcriptional and translational events. Inhibition of tyrosine phosphorylation, by herbimycin A, blocked crystal-induced COX-2. Similarly, an inhibitor of the p38 mitogen-activated protein kinase, SB 203580, inhibited the stimulation of COX-2. Colchicine inhibited crystal-induced COX-2. In all cases, prostanoid synthesis was concomitantly inhibited. Taken together, these results implicate COX-2 in the development of MSU-induced inflammation.
尿酸单钠（MSU）微晶在关节及关节周围组织中的形成与沉积是导致被称为痛风性关节炎的急性或慢性炎症反应的致病因素。单核吞噬细胞激活参与痛风发作的早期触发事件。由于受刺激的单核吞噬细胞可构成诱导型环氧化酶（COX-2）的重要来源，我们评估了促炎微晶对晶体刺激的单核细胞中COX-2蛋白表达可能产生的影响。我们发现，MSU晶体而非二水焦磷酸钙（CPPD）晶体可诱导COX-2，这与前列腺素E2（PGE2）和血栓素A2（TXA2）的合成相关。晶体诱导的COX-2从头合成依赖于转录和翻译过程。除草霉素A抑制酪氨酸磷酸化可阻断晶体诱导的COX-2。同样，p38丝裂原活化蛋白激酶抑制剂SB 203580可抑制COX-2的刺激。秋水仙碱可抑制晶体诱导的COX-2。在所有情况下，类前列腺素合成均同时受到抑制。综上所述，这些结果表明COX-2参与了MSU诱导的炎症发展。
