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首页> 外文期刊>Osteoarthritis and cartilage >Diacerhein and rhein reduce the ICE-induced IL-1beta and IL-18 activation in human osteoarthritic cartilage.
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Diacerhein and rhein reduce the ICE-induced IL-1beta and IL-18 activation in human osteoarthritic cartilage.

机译：泛黄素和大黄酸可降低ICE诱导的人骨关节炎软骨中的IL-1beta和IL-18活化。

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OBJECTIVE: IL-1beta plays a fundamental role in osteoarthritis (OA) pathophysiology and cartilage destruction. Targeting the activation mechanism of this cytokine appears to be important as a therapeutic approach. As the interleukin-1 converting enzyme (ICE) is the physiologic modulator of the production of active IL-1beta, we investigated the effect of diacerhein and its active metabolite rhein used in the treatment of OA patients, on the enzyme expression and synthesis on human OA cartilage. Further, we looked at the effect of both drugs on the production of the active form of IL-1beta and IL-18. METHODS: The expression and synthesis of ICE were investigated on human OA cartilage explants using in-situ hybridization and immunohistochemical methods, respectively. The effect of the drugs on ICE OA chondrocytes was also determined by Northern blotting and a specific ELISA assay. Furthermore, the effect of both drugs on the level of active IL-1beta and IL-18 was examined by immunohistochemistry. RESULTS: Data showed that diacerhein and rhein have no true effect on reducing total ICE mRNA by both Northern blotting analysis and in-situ hybridization. A marked and statistically significant decrease was, however, found for protein production. ELISA showed a reduction of 31% (P< 0.04) for diacerhein and 50% (P< 0.02) for rhein. The drugs' immunohistological cell score reduction was similar to data from the ELISA, and a statistical significant reduction of ICE production was found at both superficial and deep zones of the cartilage. IL-1beta and IL-18 were both preferentially produced in chondrocytes of the superficial zone. For each of these cytokines, both drugs demonstrated a statistically significant decrease in this zone. A marked decrease was also noted in the deep zone, but statistical significance was reached only for rhein. CONCLUSION: These results provide a novel regulatory mechanism by which diacerhein and rhein could exert a down-regulation on IL-1's effect on OA cartilage.
机译：目的：IL-1β在骨关节炎（OA）的病理生理和软骨破坏中起着重要作用。靶向这种细胞因子的激活机制作为治疗方法似乎很重要。由于白介素-1转换酶（ICE）是产生活性IL-1beta的生理调节剂，因此我们研究了diacerhein及其活性代谢产物大黄酸对OA患者的治疗对人体内酶表达和合成的影响OA软骨。此外，我们研究了两种药物对IL-1beta和IL-18活性形式产生的影响。方法：采用原位杂交和免疫组化方法研究人骨软骨外植体中ICE的表达和合成。还通过Northern印迹和特异性ELISA测定来确定药物对ICE OA软骨细胞的作用。此外，通过免疫组织化学检查了两种药物对活性IL-1β和IL-18水平的影响。结果：数据显示，通过Northern印迹分析和原位杂交，腹泻素和大黄酸对减少总ICE mRNA没有真正作用。然而，发现蛋白质生产显着且统计学上显着的下降。酶联免疫吸附测定显示，对于泛黄素而言，降低了31％（P <0.04），对于大黄酸而言则降低了50％（P <0.02）。药物的免疫组织学细胞分数降低与ELISA数据相似，并且在软骨的浅表和深部均发现ICE产生统计显着降低。 IL-1beta和IL-18都优先在浅表区的软骨细胞中产生。对于这些细胞因子中的每一种，两种药物均显示该区域的统计学显着降低。在深部区域也注意到明显的减少，但是仅对于大黄酸达到统计学显着性。结论：这些结果提供了一种新的调节机制，通过该调节机制，泛黄素和大黄酸可以下调IL-1对OA软骨的作用。

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