Cardiotrophin-1 induces intercellular adhesion molecule-1 expression by nuclear factor κB activation in human umbilical vein endothelial cells  

作　　者：Michael Fritzenwanger Martin Foerster Katharina Meusel Christian Jung Hans R. Figulla 

机构地区：[1]Department of Internal Medicine I, Friedrich-Schiller-University Jena, Erlanger Allee 101, 07740 Jena, Germany

出　　处：《Chinese Medical Journal》2008年第24期2592-2598,共7页中华医学杂志（英文版）

摘　　要：Background In addition to elevated concentrations of cytokines, patients with congestive endothelial dysfunction and increased plasma concentrations of adhesion molecules heart failure （CHF） show ke intercellular adhesion molecule-1 （ICAM-1）. Furthermore, the concentration of cardiotrophin-1 （CT-1） - a cytokine of the interleukin-6 superfamily - is increased in CHF. We tested the hypothesis whether CT-1 is able to induce ICAM-1 in human umbilical vein endothelial cells （HUVEC）. Furthermore we examined the signalling mechanisms of CT-1 mediated ICAM-1 expression. Methods Confluent layers of HUVEC were incubated with increasing concentrations of CT-1 （5 to 100 ng/ml） for different periods. ICAM-1 mRNA was determined by real-time polymerase chain reaction （PCR） and ICAM-1 surface expression by fluorescence-activated cell sorter （FACS） analysis and soluble ICAM-1 （slCAM-1） in the culture supernatant by enzyme linked immunosorbent assay （ELISA）. To clarify the signalling pathway of CT-1 induced ICAM-1 expression we used various inhibitors of possible signal transducing molecules, electromobility shift assay （EMSA） and Western blot analysis. Results CT-1 induced ICAM-1 mRNA （1.8±0.8 fold increase compared to unstimulated cells after 6 hours） and protein （1.4±0.2 fold increase compared to unstimulated cells after 48 hours） in HUVEC in a time- and concentration-dependent manner. EMSA experiments show that CT-1 causes nuclear factor （NF） κB activation. Because parthenolide could inhibit CT-1 induced ICAM-1 expression NFκB activation is required in this pathway. CT-1 did not activate extracellular signal regulated kinases （ERK）, c-Jun N-terminal kinase （JNK） and p38. Conclusion CT-1 is able to induce ICAM-1 in endothelial cells by NFκB activation. These results may explain in part elevated ICAM-1 concentrations in patients with CHF and endothelial dysfunction.Background In addition to elevated concentrations of cytokines, patients with congestive endothelial dysfunction and increased plasma concentrations of adhesion molecules heart failure （CHF） show ke intercellular adhesion molecule-1 （ICAM-1）. Furthermore, the concentration of cardiotrophin-1 （CT-1） - a cytokine of the interleukin-6 superfamily - is increased in CHF. We tested the hypothesis whether CT-1 is able to induce ICAM-1 in human umbilical vein endothelial cells （HUVEC）. Furthermore we examined the signalling mechanisms of CT-1 mediated ICAM-1 expression. Methods Confluent layers of HUVEC were incubated with increasing concentrations of CT-1 （5 to 100 ng/ml） for different periods. ICAM-1 mRNA was determined by real-time polymerase chain reaction （PCR） and ICAM-1 surface expression by fluorescence-activated cell sorter （FACS） analysis and soluble ICAM-1 （slCAM-1） in the culture supernatant by enzyme linked immunosorbent assay （ELISA）. To clarify the signalling pathway of CT-1 induced ICAM-1 expression we used various inhibitors of possible signal transducing molecules, electromobility shift assay （EMSA） and Western blot analysis. Results CT-1 induced ICAM-1 mRNA （1.8±0.8 fold increase compared to unstimulated cells after 6 hours） and protein （1.4±0.2 fold increase compared to unstimulated cells after 48 hours） in HUVEC in a time- and concentration-dependent manner. EMSA experiments show that CT-1 causes nuclear factor （NF） κB activation. Because parthenolide could inhibit CT-1 induced ICAM-1 expression NFκB activation is required in this pathway. CT-1 did not activate extracellular signal regulated kinases （ERK）, c-Jun N-terminal kinase （JNK） and p38. Conclusion CT-1 is able to induce ICAM-1 in endothelial cells by NFκB activation. These results may explain in part elevated ICAM-1 concentrations in patients with CHF and endothelial dysfunction.

关 键 词：CARDIOTROPHIN-1 intercellular adhesion molecule-1 nuclear factor κB human umbilical vein endothelial cells 

分 类 号：R543[医药卫生—心血管疾病]