INVIVO CYCLOOXYGENASE EXPRESSION IN SYNOVIAL TISSUES OF PATIENTS WITH RHEUMATOID-ARTHRITIS AND OSTEOARTHRITIS AND RATS WITH ADJUVANT AND STREPTOCOCCAL CELL-WALL ARTHRITIS
INVIVO CYCLOOXYGENASE EXPRESSION IN SYNOVIAL TISSUES OF PATIENTS WITH RHEUMATOID-ARTHRITIS AND OSTEOARTHRITIS AND RATS WITH ADJUVANT AND STREPTOCOCCAL CELL-WALL ARTHRITIS
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DOI：
10.1172/jci115591
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发表时间：
1992-01-01
影响因子：
15.9
通讯作者：
WILDER, RL
中科院分区：
文献类型：
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作者：
SANO, H;HLA, T;WILDER, RL
环氧合酶(COX)，或前列腺素(PG)H合成酶，在炎症性疾病中发挥作用，但关于COX在体内的调节数据非常有限。因此，我们研究了COX在类风湿关节炎(RA)和骨关节炎(OA)患者的滑液以及链球菌细胞壁(SCW)和佐剂性关节炎大鼠关节中的体内表达。RA滑膜细胞内广泛而强烈的COX免疫染色与单个核细胞浸润的程度和强度有关。在骨性关节炎和正常人滑膜中的染色明显较少或不明确。同样，COX免疫染色在正常和关节炎抵抗的F344/N大鼠的关节中也是不明确的。相反，雌性Lewis(LEW/N)大鼠的高水平表达迅速发展，遍及后肢关节和覆盖组织，包括皮肤，先于或平行于临床明显的实验性关节炎。在注射SCW或佐剂后2~4d，裸鼠LW、RNU/RNU大鼠关节中可见COX的表达，但表达不明显。生理剂量的抗炎糖皮质激素，而不是黄体酮，抑制了LEW/N大鼠的关节炎和COX的表达。这些观察表明，在体内，(A)COX的表达在炎症性关节疾病中上调，(B)其表达水平受基因控制，并与疾病严重程度有关，(C)持续的高水平上调依赖于T细胞，以及(D)抗炎糖皮质激素下调其表达。
Cyclooxygenase (COX), or prostaglandin (PG) H synthase, plays a role in inflammatory diseases, but very limited data exist on the regulation of COX in vivo. We, therefore, studied the in vivo expression of COX in synovia from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), as well as joints of rats with streptococcal cell wall (SCW) and adjuvant arthritis. Extensive and intense intracellular COX immunostaining, which correlated with the extent and intensity of mononuclear cell infiltration, was observed in cells throughout RA synovia. Significantly less or equivocal staining was noted in OA and normal human synovia. Similarly, COX immunostaining was equivocal in the joints of normal and arthritis-resistant F344/N rats. In contrast, high level expression developed rapidly in euthymic female Lewis (LEW/N) rats throughout the hindlimb joints and overlying tissues including skin, preceding or paralleling clinically apparent experimental arthritis. COX was expressed in the joints of athymic LEW.rnu/rnu rats 2-4 d after injection of SCW or adjuvant but was not sustained. Physiological doses of antiinflammatory glucocorticoids, but not progesterone, suppressed both arthritis and COX expression in LEW/N rats. These observations suggest that, in vivo, (a) COX expression is upregulated in inflammatory joint diseases, (b) the level of expression is genetically controlled and is a biochemical correlate of disease severity, (c) sustained high level up-regulation is T cell dependent, and (d) expression is down-regulated by antiinflammatory glucocorticoids.