Liu S W, Qiao S B, Yuan J S, Liu D Q
Department of Cardiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Horm Metab Res. 2009 Apr;41(4):281-6. doi: 10.1055/s-0028-1102914. Epub 2008 Nov 13.
Monocyte chemotactic protein-1 and interleukin-6 are important inflammatory cytokines, which have close relationships with atherosclerosis. Visfatin is a novel adipokine involved in regulation of inflammatory cytokines, however, associations of visfatin with cytokines (MCP-1, IL-6) in human umbilical vein endothelial cells are unclear. The aim of this study was to determine whether visfatin has effects on the expression of MCP-1 and IL-6 in human umbilical vein endothelial cells. Enzyme-linked immunosorbent assay were used for measuring MCP-1 and IL-6 production in human umbilical vein endothelial cells. Real-time quantitative reverse-transcription polymerase chain reaction was used for determining MCP-1 and IL-6 mRNA expression. For the pathway determination following inhibitors were used: wortmannin [phosphatiylinositol 3-kinase (PI3K)], SB203580 [p38 mitogen-activated protein kinase (MAPK)], PD98059 [extracellular signal-regulated kinase (ERK) 1/2)], JNK inhibitor II [c-Jun NH 2-terminal kinase (JNK)]. We demonstrated that visfatin could obviously upregulate secretion of MCP-1and IL-6 in a dose- and time-dependent manner in human umbilical vein endothelial cells. Visfatin-induced effects were diminished by SB203580, wortmannin, and PD98059. In summary, these results suggest that visfatin-induced MCP-1 and IL-6 production involve p38 MAPK, PI3K, and ERK 1/2 pathways in human umbilical vein endothelial cells as determined by inhibition with specific inhibitors.
单核细胞趋化蛋白-1和白细胞介素-6是重要的炎性细胞因子，它们与动脉粥样硬化关系密切。内脂素是一种参与调节炎性细胞因子的新型脂肪因子，然而，内脂素与人脐静脉内皮细胞中细胞因子（MCP-1、IL-6）的关联尚不清楚。本研究的目的是确定内脂素是否对人脐静脉内皮细胞中MCP-1和IL-6的表达有影响。采用酶联免疫吸附测定法检测人脐静脉内皮细胞中MCP-1和IL-6的产生。采用实时定量逆转录聚合酶链反应测定MCP-1和IL-6 mRNA的表达。为了确定相关信号通路，使用了以下抑制剂：渥曼青霉素[磷脂酰肌醇3激酶（PI3K）]、SB203580 [p38丝裂原活化蛋白激酶（MAPK）]、PD98059 [细胞外信号调节激酶（ERK）1/2]、JNK抑制剂II [c-Jun氨基末端激酶（JNK）]。我们证明，内脂素能以剂量和时间依赖性方式明显上调人脐静脉内皮细胞中MCP-1和IL-6的分泌。SB203580、渥曼青霉素和PD98059可减弱内脂素诱导的效应。总之，这些结果表明，通过特异性抑制剂抑制实验确定，内脂素诱导人脐静脉内皮细胞产生MCP-1和IL-6涉及p38 MAPK、PI3K和ERK 1/2信号通路。
