Stretch-induced IL-6 secretion from endothelial cells requires NF-kappaB activation.

Stretch-induced IL-6 secretion from endothelial cells requires NF-kappaB activation.
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DOI:
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发表时间:
2003
影响因子:
3.1
通讯作者:
Satoshi Kobayashi;M. Nagino;S. Komatsu;K. Naruse;Y. Nimura;M. Nakanishi;M. Sokabe
Satoshi Kobayashi;M. Nagino;S. Komatsu;K. Naruse;Y. Nimura;M. Nakanishi;M. Sokabe
中科院分区:
生物学4区
文献类型:
--
作者:
Satoshi Kobayashi;M. Nagino;S. Komatsu;K. Naruse;Y. Nimura;M. Nakanishi;M. Sokabe

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内皮细胞 (EC) 响应机械刺激而分泌白介素 6 (IL-6),在再生和炎症反应中发挥重要作用。本研究的目的是确定 EC 响应单轴连续拉伸分泌 IL-6 的机制。连续拉伸诱导人脐静脉内皮细胞 (HUVEC) 以剂量依赖性方式分泌 IL-6。逆转录聚合酶链反应(RT-PCR)扩增显示IL-6基因的转录在拉伸后2小时达到峰值。 IkappaB 激酶 (IKK) 活性的体外激酶测定表明,IKK 的激活在拉伸后 15 分钟达到峰值。两种 NF-kappaB 抑制剂吡咯烷二硫代氨基甲酸酯 (PDTC) 和 SN50,或 NF-kappaB p65 和 p50 的反义寡脱氧核苷酸抑制连续拉伸诱导的 IL-6 mRNA 表达。总之,连续拉伸诱导 EC 分泌 IL-6,很可能是通过连续激活 IKK 和 NF-κB。
Interleukin-6 (IL-6) secretion from endothelial cells (ECs) in response to mechanical stimuli plays an important role in the regenerative and inflammatory responses. The aim of this study was to determine the mechanism for the secretion of IL-6 from ECs in response to uni-axial continuous stretch. Continuous stretch induced IL-6 secretion from human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Reverse transcriptase-polymerase chain reaction (RT-PCR) amplification showed that the transcription of the IL-6 gene peaked 2h after stretch. In vitro kinase assay of IkappaB kinase (IKKs) activity demonstrated that the activation of IKKs peaked 15 min after stretch. Two NF-kappaB inhibitors, pyrrolidine dithiocarbamanate (PDTC) and SN50, or antisense oligodeoxynucleotides for NF-kappaB p65 and p50 suppressed IL-6 mRNA expressions induced by continuous stretch. In conclusion, continuous stretch induces IL-6 secretion from ECs, most likely through sequential activation of IKKs and NF-kappaB.