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• W2031011447 endingPage "51" @default.
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• W2031011447 abstract "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 NFκB—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-κB 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." @default.
• W2031011447 created "2016-06-24" @default.
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• W2031011447 date "2006-01-07" @default.
• W2031011447 modified "2023-09-27" @default.
• W2031011447 title "Cardiotrophin-1 induces monocyte chemoattractant protein-1 synthesis in human umbilical vein endothelial cells" @default.
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• W2031011447 doi "https://doi.org/10.1016/j.cyto.2005.11.016" @default.
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