壳寡糖通过抑制 p38 和 Akt 蛋白激酶抑制脂多糖诱导的人脐静脉内皮细胞 IL-8 的表达。
Chitosan oligosaccharides suppress LPS-induced IL-8 expression in human umbilical vein endothelial cells through blockade of p38 and Akt protein kinases.
机构信息
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
出版信息
Acta Pharmacol Sin. 2011 Apr;32(4):478-86. doi: 10.1038/aps.2011.10.
AIM
To investigate whether and how COS inhibited IL-8 production in LPS-induced human umbilical vein endothelial cells (HUVECs).
METHODS
RT-PCR, enzyme-linked immunosorbent assays (ELISA) and Western blotting were used to study IL-8 expression and related signaling pathway. Wound healing migration assays and monocytic cell adhesion analysis were used to explore the chemotactic and adhesive activities of HUVECs.
RESULTS
COS 50-200 μg/mL exerted a significant inhibitory effect on LPS 100 ng/mL-induced IL-8 expression in HUVECs at both the transcriptional and translational levels. In addition, COS 50-200 μg/mL inhibited LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs in a concentration-dependent manner. Signal transduction studies suggest that COS blocked LPS-induced activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) and phosphokinase Akt. Further, the over-expression of LPS-induced IL-8 mRNA in HUVECs was suppressed by a p38 MAPK inhibitor (SB203580, 25 μmol/L) or a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002, 50 μmol/L).
CONCLUSION
COS inhibited LPS-induced IL-8 expression in HUVECs through the blockade of the p38 MAPK and PI3K/Akt signaling pathways.
目的
研究 COS 是否以及如何抑制 LPS 诱导的人脐静脉内皮细胞（HUVEC）中 IL-8 的产生。
方法
采用 RT-PCR、酶联免疫吸附试验（ELISA）和 Western blot 检测 IL-8 表达及相关信号通路。采用划痕愈合迁移实验和单核细胞黏附分析探讨 HUVEC 的趋化和黏附活性。
结果
COS 50-200μg/ml 在转录和翻译水平上对 LPS 100ng/ml 诱导的 HUVECs 中 IL-8 表达均具有显著的抑制作用。此外，COS 50-200μg/ml 呈浓度依赖性抑制 LPS 诱导的 HUVEC 迁移和 U937 单核细胞黏附至 HUVEC。信号转导研究表明，COS 阻断了 LPS 诱导的核因子-κB（NF-κB）和激活蛋白-1（AP-1）的激活以及丝裂原活化蛋白激酶（MAPK）p38 和磷酸化蛋白激酶 Akt 的磷酸化。此外，p38 MAPK 抑制剂（SB203580，25μmol/L）或磷脂酰肌醇 3-激酶（PI3K）抑制剂（LY294002，50μmol/L）抑制 LPS 诱导的 HUVECs 中 IL-8mRNA 的过度表达。
结论
COS 通过阻断 p38 MAPK 和 PI3K/Akt 信号通路抑制 LPS 诱导的 HUVECs 中 IL-8 的表达。
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