Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways
Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways
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DOI：
10.1007/s00011-009-0118-3
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发表时间：
2010-06-01
影响因子：
6.7
通讯作者：
Yu, Chao
中科院分区：
文献类型：
--
作者：
Liu, Hong-Tao;He, Jun-Lin;Yu, Chao
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（HUVECs）产生白细胞介素-6（IL-6）和白细胞介素-8（IL-8）的抑制作用。采用逆转录-聚合酶链反应（RT-PCR）和酶联免疫吸附试验（ELISA）检测IL-6和IL-8的mRNA和蛋白水平。采用单层伤口愈合实验和单核细胞粘附实验研究LPS诱导的HUVEC迁移和单核细胞与HUVEC的粘附。Western印迹法检测核因子kappa B（NF-κ B）、抑制因子kappa B-alpha（I kappa B-alpha）、p38丝裂原活化蛋白激酶（MAPK）和ERK 1/2的表达，栀子苷在转录和翻译水平上有效抑制脂多糖诱导的HUVEC 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单核细胞粘附HUVEC。信号转导研究表明，京尼平苷可阻断LPS诱导的HUVECs NF-κ B活化、I κ B-α降解、p38 MAPK和ERK 1/2磷酸化，从而抑制LPS诱导的HUVECs产生IL-6和IL-8。
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).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 kappa B (NF-kappa B), inhibitory factor kappa B-alpha (I kappa B-alpha), p38 mitogen-activated protein kinase (MAPK) and ERK1/2 were determined by Western blot analysis.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-kappa B, degradation of I kappa B-alpha, and phosphorylation of p38 MAPK and ERK1/2 in HUVECs challenged by LPS.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.