Chrysin Attenuates IL-1β-Induced Expression of Inflammatory Mediators by Suppressing NF-κB in Human Osteoarthritis Chondrocytes
Chrysin Attenuates IL-1β-Induced Expression of Inflammatory Mediators by Suppressing NF-κB in Human Osteoarthritis Chondrocytes
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DOI：
10.1007/s10753-017-0558-9
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发表时间：
2017-08-01
期刊：
影响因子：
5.1
通讯作者：
Chen, Hua
中科院分区：
文献类型：
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作者：
Zheng, Wenhao;Tao, Zhenyu;Chen, Hua
骨关节炎（OA）是一种以软骨退化和炎症为特征的退行性关节疾病。蜂蜜素是一种从蜂蜜和蜂蜜中提取的天然黄酮类化合物，据报道具有抗炎作用。然而，白杨素对OA的抗炎作用尚未报道。本研究旨在评估白杨素对人OA软骨细胞的影响。用白杨素（1、5、10 μ M）预处理人OA软骨细胞2小时，随后用IL-1 β刺激24小时。通过Griess反应和ELISA评价NO、PGE 2、MMP-1、MMP-3、MMP-13、ADAMTS-4和ADAMTS-5的产生。实时定量PCR检测考克斯-2、iNOS、MMP-1、MMP-3、MMP-13、ADAMTS-4、ADAMTS-5、聚集蛋白聚糖和II型胶原的mRNA表达。Western blot检测考克斯-2、iNOS、p65、p-p65、I κ B-α、p-I κ B-α蛋白的表达。免疫荧光法检测Ⅱ型胶原蛋白和p65核转位蛋白的表达。我们发现白杨素显著抑制IL-1 β诱导的NO和PGE 2的产生;抑制考克斯-2、iNOS、MMP-1、MMP-3、MMP-13、ADAMTS-4和ADAMTS-5的表达;以及抑制聚集蛋白聚糖和II型胶原的降解。此外，白杨素显著阻断IL-1 β刺激的I κ B-α降解和NF-κ B活化。综上所述，这些结果表明白杨素可能是治疗OA的潜在药物。
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Chrysin, a natural flavonoid extracted from honey and propolis, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of chrysin on OA have not been reported. This study aimed to assess the effects of chrysin on human OA chondrocytes. Human OA chondrocytes were pretreated with chrysin (1, 5, 10 mu M) for 2 h and subsequently stimulated with IL-1 beta for 24 h. Production of NO, PGE2, MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 was evaluated by the Griess reaction and ELISAs. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and collagen-II was measured by real-time PCR. The protein expression of COX-2, iNOS, p65, p-p65, I kappa B-alpha, and p-I kappa B-alpha was detected by Western blot. The protein expression of collagen-II and p65 nuclear translocation was evaluated by immunofluorescence. We found that chrysin significantly inhibited the IL-1 beta-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, chrysin dramatically blocked IL-1 beta-stimulated I kappa B-alpha degradation and NF-kappa B activation. Taken together, these results suggest that chrysin may be a potential agent in the treatment of OA.