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首页> 外文期刊>Rheumatology >Delphinidin inhibits IL-1β-induced activation of NF-κB by modulating the phosphorylation of IRAK-1Ser376 in human articular chondrocytes
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Delphinidin inhibits IL-1β-induced activation of NF-κB by modulating the phosphorylation of IRAK-1Ser376 in human articular chondrocytes

机译：Delphinidin通过调节人关节软骨细胞中IRAK-1Ser376的磷酸化来抑制IL-1β诱导的NF-κB活化

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摘要

Objective: In OA, there is enhanced expression of pro-inflammatory cytokines such as IL-1β in the affected joint. Delphinidin, an anthocyanidin found in pigmented fruits and vegetables, has been shown to possess anti-inflammatory and antioxidant properties. In the present study we determined whether delphinidin would inhibit the IL-1β-induced activation of NF-κB in human chondrocytes and determined the mechanism of its action. Methods: PGE2 levels and activation of NF-κB p65 in human OA chondrocytes were determined by ELISA-based assays. Protein expression of cyclo-oxygenase-2 (COX-2) and phosphorylation of kinases was determined by western immunoblotting. Expression level of mRNAs was determined by TaqMan assays. Results: Delphinidin inhibited IL-1β-induced expression of COX-2 and production of PGE2 in human chondrocytes. Delphinidin also inhibited IL-1β-mediated phosphorylation of IL-1 receptor-associated kinase-1Ser376, phosphorylation of IKKα/β, expression of IKKβ, degradation of IκBα, and activation and nuclear translocation of NF-κB/p65. Phosphorylation of TGF-β-activated kinase 1 was not observed but NF-κB-inducing kinase (NIK) was phosphorylated and phosphorylation of NIK was blocked by delphinidin in IL-1β-treated human chondrocytes. Conclusion: These data identify delphinidin as a novel inhibitor of IL-1β-induced production of cartilage-degrading molecule PGE2 via inhibition of COX-2 expression and provide new insight into the mechanism of its action. Our results also identify inhibition of IRAK1Ser376 phosphorylation by delphinidin in IL-1β-induced activation of NF-kB in human chondrocytes. Given the important role played by IL-1β-induced NF-κB activation, COX-2 expression and PGE2 production in OA, our results may have important implications for the development of novel therapeutic strategies for the prevention/treatment of OA.
机译：目的：在OA中，受影响的关节中促炎性细胞因子如IL-1β的表达增强。 Delphinidin是一种在有色水果和蔬菜中发现的花青素，已被证明具有抗炎和抗氧化的特性。在本研究中，我们确定了飞燕草碱是否会抑制IL-1β诱导的人软骨细胞中NF-κB的活化，并确定了其作用机理。方法：采用ELISA法检测人骨关节炎软骨细胞中PGE2的水平及NF-κBp65的活化。通过western免疫印迹法确定了环氧合酶2（COX-2）的蛋白表达和激酶的磷酸化。通过TaqMan测定法确定mRNA的表达水平。结果：Delphinidin抑制人软骨细胞中IL-1β诱导的COX-2表达和PGE2的产生。 Delphinidin还抑制IL-1β介导的IL-1受体相关激酶1Ser376的磷酸化，IKKα/β的磷酸化，IKKβ的表达，IκBα的降解以及NF-κB/ p65的活化和核易位。在IL-1β处理的人软骨细胞中，未观察到TGF-β激活的激酶1的磷酸化，但NF-κB诱导激酶（NIK）被磷酸化，NIK的磷酸化被飞燕草素阻断。结论：这些数据确定了德尔菲尼丁是一种通过抑制COX-2表达而成为IL-1β诱导的软骨降解分子PGE2产生的新型抑制剂，并为其作用机理提供了新见解。我们的研究结果还确定了在人软骨细胞中IL-1β诱导的NF-kB活化中，delphinidin对IRAK1Ser376磷酸化的抑制作用。考虑到IL-1β诱导的OA中IL-1β诱导的NF-κB活化，COX-2表达和PGE2产生的重要作用，我们的结果可能对开发预防/治疗OA的新治疗策略具有重要意义。

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