Cardiotrophin-1 induces monocyte chemoattractant protein-1 synthesis in human umbilical vein endothelial cells

被引：13

作者：

Fritzenwanger, M ^{[1
]}

Kuethe, F ^{[1
]}

Haase, D ^{[1
]}

Jandt, E ^{[1
]}

Figulla, HR ^{[1
]}

机构：

[1] Univ Jena, Div Cardiol, Dept Internal Med 1, D-07740 Jena, Germany

来源：

CYTOKINE | 2006年 / 33卷 / 01期

关键词：

cardiotrophin-1; monocyte chemoattractant protein-1; chronic heart failure;

D O I：

10.1016/j.cyto.2005.11.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In chronic heart failure (CHF) cardiotrophin-1 (CT-1) and monocyte chemoattractant protein-1 (MCP-1) plasma concentrations are elevated. CT-1 is a cytokine of the interleukin-6 (IL-6) superfamily. Most members of the IL-6 family are able to activate human umbilical vein endothelial cells (HUVEC) but so far there are no data which demonstrate that CT-1 can activate HUVEC. Because MCP-1-as a marker of endothelial activation-is elevated in CHF we examined whether CT-1 will induce MCP-1 production in HUVEC. MCP-1 mRNA levels were determined by real time PCR, RT-PCR and northern blot analysis and MCP-1 protein concentrations in the supernatant by ELISA. Signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (pSTAT3) were investigated by western blot analysis. Incubation of HUVEC with different CT-1 concentrations for various time periods induced time and concentration dependent MCP-1 mRNA. Maximal MCP-1 mRNA was reached after 6 h. After 24 h CT-1 caused a significant induction of MCP-1 protein in the supernatant compared to control. CT-1 induced concentration dependent phosphorylation of STAT3 without any change in total-STAT3 concentration. Piceatannol-a specific blocker of STAT3 phosphorylation-inhibited CT-1 induced MCP-1 induction completely. AG490-a blocker of the JAK2 pathway-was also able to inhibit CT-1 induced MCP-1 upregulation, indicating that the JAK2 pathway is also necessary for MCP-1 induction. Parthenolide-a blocker of NF kappa B-inhibited CT-1 induced MCP-1 expression, completely. Our data show that CT-1 induces in a concentration and time dependent manner MCP-1 mRNA and protein in HUVEC. STAT3 phosphorylation, the activation of JAK2 and NF-kappa B are involved in this pathway. In CHF, CT-1 may be able to induce MCP-1 which might be responsible for progression of heart failure either by recruiting inflammatory cells within the myocardium or by a direct modulation of myocyte function. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：46 / 51

页数：6

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