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栀子苷通过阻断 p38 和 ERK1/2 信号通路抑制脂多糖诱导的人脐静脉内皮细胞白细胞介素-6 和白细胞介素-8 的产生。

Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways.

机构信息

Institute of Life Sciences, Chongqing Medical University, 1 Yi Xue Yuan Road, Box 174, 400016 Chongqing, People's Republic of China.

出版信息

Inflamm Res. 2010 Jun;59(6):451-61. doi: 10.1007/s00011-009-0118-3. Epub 2009 Nov 29.

DOI:10.1007/s00011-009-0118-3
PMID:20091087
Abstract

OBJECTIVE

The aim of this study was to investigate the inhibitory effect of geniposide on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and interleukin-8 (IL-8) production in human umbilical vein endothelial cells (HUVECs).

MATERIALS AND METHODS

Primary HUVECs were used. The mRNA/protein levels of IL-6 and IL-8 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). LPS-induced HUVEC migration and adhesion of monocytes to HUVECs were studied by monolayer wound healing experiments and monocytic cell adhesion assay, respectively. Expression of nuclear factor kappaB (NF-kappaB), inhibitory factor kappaB-alpha (IkappaB-alpha), p38 mitogen-activated protein kinase (MAPK) and ERK1/2 were determined by Western blot analysis.

RESULTS

Geniposide effectively inhibited LPS-induced expression of IL-6 and IL-8 in HUVECs at the transcription and translation levels. Additionally, geniposide suppressed LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs. Signal transduction studies indicate that geniposide blocked the activation of NF-kappaB, degradation of IkappaB-alpha, and phosphorylation of p38 MAPK and ERK1/2 in HUVECs challenged by LPS.

CONCLUSION

The results show that geniposide can inhibit LPS-induced IL-6 and IL-8 production in HUVECs by blocking p38 MAPK and ERK1/2 signaling pathways.

摘要

目的

本研究旨在探讨京尼平苷对脂多糖(LPS)诱导的人脐静脉内皮细胞(HUVEC)白细胞介素 6(IL-6)和白细胞介素 8(IL-8)产生的抑制作用。

材料和方法

使用原代 HUVEC。通过逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附试验(ELISA)测定 IL-6 和 IL-8 的 mRNA/蛋白水平。通过单层划痕愈合实验和单核细胞黏附实验分别研究 LPS 诱导的 HUVEC 迁移和单核细胞黏附到 HUVECs 的能力。通过 Western blot 分析测定核因子 kappaB(NF-kappaB)、抑制因子 kappaB-α(IkappaB-α)、p38 丝裂原活化蛋白激酶(p38 MAPK)和 ERK1/2 的表达。

结果

京尼平苷在转录和翻译水平上有效抑制 LPS 诱导的 HUVEC 中 IL-6 和 IL-8 的表达。此外,京尼平苷抑制 LPS 诱导的 HUVEC 迁移和 U937 单核细胞黏附到 HUVECs。信号转导研究表明,京尼平苷阻断了 LPS 刺激的 HUVEC 中 NF-kappaB 的激活、IkappaB-α 的降解以及 p38 MAPK 和 ERK1/2 的磷酸化。

结论

结果表明,京尼平苷通过阻断 p38 MAPK 和 ERK1/2 信号通路抑制 LPS 诱导的 HUVEC 中 IL-6 和 IL-8 的产生。

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