金硫代苹果酸和羟氯喹啉可抑制软骨细胞及人骨关节炎软骨中一氧化氮的产生。

Aurothiomalate and hydroxychloroquine inhibit nitric oxide production in chondrocytes and in human osteoarthritic cartilage.

作者信息

Vuolteenaho K, Kujala P, Moilanen T, Moilanen E

机构信息

The Immunopharmacological Research Group, Medical School, University of Tampere, Tampere University Hospital, Finland.

出版信息

Scand J Rheumatol. 2005 Nov-Dec;34(6):475-9. doi: 10.1080/03009740510026797.

DOI:10.1080/03009740510026797

PMID:16393772

Abstract

OBJECTIVES

Nitric oxide (NO) is a destructive mediator produced by activated chondrocytes. The aim of the present study was to investigate the effect of disease-modifying anti-rheumatic drugs (DMARDs) on interleukin-1beta (IL-1beta)-induced NO production in chondrocyte cultures, and in human osteoarthritic cartilage.

RESULTS

Aurothiomalate, hydroxychloroquine, methotrexate and leflunomide inhibited IL-1beta-induced inducible NO synthase (iNOS) expression and NO production in immortalized H4 chondrocytes, while penicillamine and sulfasalazine had no effect. This can be explained by the fact that the four effective DMARDs also suppressed IL-1beta-induced activation of nuclear factor kappa B (NF-kappaB), which is a crucial transcription factor for iNOS. Aurothiomalate and hydroxychloroquine also inhibited IL-1beta-induced NO production in OA cartilage whereas methotrexate and leflunomide had no effect.

CONCLUSION

Aurothiomalate and hydroxychloroquine suppressed IL-1beta-induced NO production in chondrocyte cultures and in OA cartilage. The results suggest an additional anti-inflammatory mechanism for aurothiomalate and hydroxychloroquine and indicates their possible therapeutic value in the treatment of osteoarthritis (OA).

摘要

目的

一氧化氮（NO）是由活化软骨细胞产生的一种破坏性介质。本研究的目的是探讨改善病情抗风湿药（DMARDs）对白细胞介素-1β（IL-1β）诱导的软骨细胞培养物及人骨关节炎软骨中NO产生的影响。

结果

金硫葡糖、羟氯喹、甲氨蝶呤和来氟米特抑制IL-1β诱导的永生化H4软骨细胞中诱导型一氧化氮合酶（iNOS）表达及NO产生，而青霉胺和柳氮磺胺吡啶无此作用。这可以通过以下事实来解释，即这四种有效的DMARDs还抑制了IL-1β诱导的核因子κB（NF-κB）激活，而NF-κB是iNOS的关键转录因子。金硫葡糖和羟氯喹也抑制IL-1β诱导的骨关节炎软骨中NO产生，而甲氨蝶呤和来氟米特无此作用。