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牛磺酸氯胺对类风湿性关节炎滑膜细胞中环氧化酶2生成的前列腺素E2合成的选择性抑制作用

Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine.

作者信息

Kontny Ewa, Rudnicka Weronika, Kowalczewski Jacek, Marcinkiewicz Janusz, Maslinski Wlodzimierz

机构信息

Department of Pathophysiology and Immunology, Institute of Rheumatology, Warsaw, Poland.

出版信息

Arthritis Rheum. 2003 Jun;48(6):1551-5. doi: 10.1002/art.10975.

DOI:10.1002/art.10975
PMID:12794822
Abstract

OBJECTIVE

To investigate the effects of taurine chloramine (Tau-Cl), a chlorinated derivative of the amino acid taurine, on the expression of cyclooxygenase (COX) isoenzymes and prostaglandin E(2) (PGE(2)) synthesis in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS).

METHODS

FLS, isolated from the synovial tissue of RA patients, were treated in vitro with either interleukin-1beta (IL-1beta; 1 ng/ml) alone or together with 200-500 microM Tau-Cl. The expression of COX isoenzymes was evaluated at both the protein (Western blotting) and the messenger RNA (mRNA) (reverse transcriptase-polymerase chain reaction) levels. The concentration of PGE(2) was measured by competitive acetylcholinesterase enzyme immunoassay.

RESULTS

Resting FLS expressed mRNA encoding both COX-1 and COX-2, but only COX-1 was present at the protein level. These cells produced negligible amounts of PGE(2). Upon stimulation with IL-1beta, elevation of COX-2, but not COX-1, mRNA and protein preceded the enhancement of PGE(2) synthesis. In the presence of 300-400 microM Tau-Cl, significant inhibition of IL-1beta-triggered COX-2 mRNA and protein, and a related decrease in PGE(2) production, was observed. In contrast, no significant changes in COX-1 mRNA and protein levels were noted.

CONCLUSION

Tau-Cl inhibits IL-1beta-triggered elevation of COX-2 and generation of PGE(2) by RA FLS. These results expand the spectrum of known antiinflammatory activities of this compound.

摘要

目的

研究牛磺酸氯胺(Tau-Cl,氨基酸牛磺酸的一种氯化衍生物)对类风湿关节炎(RA)成纤维样滑膜细胞(FLS)中环氧合酶(COX)同工酶表达及前列腺素E2(PGE2)合成的影响。

方法

从RA患者滑膜组织中分离出FLS,在体外分别用单独的白细胞介素-1β(IL-1β;1 ng/ml)或与200 - 500 μM Tau-Cl共同处理。通过蛋白质(蛋白质印迹法)和信使核糖核酸(mRNA)(逆转录-聚合酶链反应)水平评估COX同工酶的表达。采用竞争性乙酰胆碱酯酶酶免疫测定法测量PGE2的浓度。

结果

静息的FLS表达编码COX-1和COX-2的mRNA,但在蛋白质水平仅存在COX-1。这些细胞产生的PGE2量可忽略不计。在用IL-1β刺激后,COX-2而非COX-1的mRNA和蛋白质升高先于PGE2合成的增强。在存在300 - 400 μM Tau-Cl的情况下,观察到对IL-1β触发的COX-2 mRNA和蛋白质有显著抑制,以及PGE2产生相关减少。相比之下,COX-1 mRNA和蛋白质水平未观察到显著变化。

结论

Tau-Cl抑制RA FLS中IL-1β触发的COX-2升高和PGE2生成。这些结果扩展了该化合物已知抗炎活性的范围。

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