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首页> 外文期刊>International immunopharmacology >Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1 beta
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Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1 beta

机译：三种不同类抗炎药对IL-1β暴露于人骨关节炎软骨细胞的软化作用

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摘要

VA694, a promising cyclooxigenase-2 (COX-2)-inhibiting hybrid drug endowed with nitric oxide (NO) releasing properties (NO-COXIB), showed COX-2-selective inhibitory effects, associated with interesting anti-inflammatory and anti-nociceptive activities. Therefore, we studied the effects of VA694 on cartilage metabolism, in comparison with Naproxcinod, a COX inhibitor and NO donor (CINOD), and Naproxen, a traditional nonsteroidal anti-inflammatory drug (NSAID) on human osteoarthritic chondrocyte cultures. IL-1 beta-stimulated chondrocytes showed a significant decrease in cell viability (P < 0.001). VA694, Naproxcinod and Naproxen alone didn't significantly affect cell viability, while it restored cell viability in cultures stimulated by IL-1 beta. The presence of IL-1 beta determined a significant increase (P < 0.001) in PGE2 levels measured by an ELISA assay, and in COX-2 and MMP-3, -9, and -13 gene expression analyzed by RT-PCR. VA694, Naproxcinod and Naproxen, at both concentrations analyzed, significantly counteracted the negative effects induced by IL-1 beta. VA694, Naproxcinod and Naproxen pre-treatment were able to inhibit IL-1 beta-induced NF-kappa B activation, when measured as its nuclear translocation (p50 and p65 subunits). Naproxcinod and Naproxen pre-treatment didn't affect cytoplasmic NF-kappa B levels; VA694 decreased the cytoplasmic levels of both subunits. Our data suggest that VA694, Naproxcinod and Naproxen, exert anti-inflammatory and chondroprotective effects on OA chondrocytes. (C) 2015 Elsevier B.V. All rights reserved.
机译：va694，一种有前途的环氧代己酶-2（COX-2） - 抑制有一氧化氮（NO）释放性质（NO-COXIB）的杂种药物，表现出COX-2选择性抑制作用，与​​有趣的抗炎和抗伤害相关活动。因此，我们研究了VA694对软骨代谢的影响，与萘普希毒剂，COX抑制剂和任何供体（CINOD）和Naproxen，一种人骨关节炎软骨细胞培养物的传统非甾体抗炎药（NSAID）进行了比较。 IL-1β受刺激的软骨细胞显示细胞活力的显着降低（P <0.001）。 va694，单独的萘啶醇和萘普生没有显着影响细胞活力，而在IL-1β刺激的培养物中恢复细胞活力。 IL-1β的存在在通过ELISA测定和通过RT-PCR分析的COX-2和MMP-3，-9和-13基因表达测定的PGE2水平中的显着增加（P <0.001）。在分析的两种浓度下，VA694，NaProxcinod和Naproxen显着抵消了IL-1β诱导的负面影响。 VA694，NaProxcinod和Naproxen预处理能够抑制IL-1β诱导的NF-κB激活，当其核转移时（P50和P65亚基）测量。萘啶醇和萘普生预处理不影响细胞质NF-κB水平; Va694降低了两个亚基的细胞质水平。我们的数据表明，VA694，Naproxcinod和Naproxen对OA软骨细胞发挥抗炎和软骨病作用。 （c）2015 Elsevier B.v.保留所有权利。

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