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Human Vascular Endothelial Cells (human + vascular_endothelial_cell)
Selected AbstractsIL-10 inhibits endothelium-dependent T cell costimulation by up-regulation of ILT3/4 in human vascular endothelial cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Christian Abstract Effects of IL-10 on endothelium-dependent T cell activation have not been investigated in detail. We confirm expression of the IL-10 receptor and effective signaling via STAT-3 in human umbilical vein endothelial cells (HUVEC). In CD4 T cell cocultures with HUVEC, pretreatment of endothelial cells with IL-10 resulted in significant dose-dependent inhibition of CD4 T cell proliferation, which also occurred when IL-10 was removed after pretreatment before starting cocultures. Th1/Th2 polarization of proliferated T cells, endothelial nitric oxide (NO), or IL-12 production were unchanged. However, IL-10 stimulation resulted in up-regulation of SOCS-3, a negative regulator of cytokine secretion, and induction of the inhibitory surface molecules immunoglobulin-like transcript 3 and 4 (ILT3/ILT4) in EC, potentially involving glucocorticoid-induced leucine zipper (GILZ). Addition of blocking antibodies against ILT3/ILT4 to EC/T cell cocultures resulted in nearly complete reestablishment of T cell proliferation. In contrast, addition of soluble ILT3 or overexpression of ILT3 in cocultures significantly reduced T cell proliferation. No induction of foxp3+ regulatory T cells was seen. In conclusion, the T cell costimulatory potential of human EC is markedly suppressed by IL-10 due to up-regulation of ILT3/ILT4, obviously not involving generation of Treg. This identifies a novel action of IL-10 in EC and a potential therapeutical target for local immunomodulation. [source] Role of transcription factor Ets-1 in the apoptosis of human vascular endothelial cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2001Kazuhide Teruyama Transcription factor Ets-1 is induced in endothelial cells (ECs) by angiogenic factors, and promotes angiogenesis by inducing angiogenesis-related genes such as MMPs and integrin ,3. Here, we examined the effect of Ets-1 on apoptosis in ECs. Overexpression of Ets-1 in human umbilical vein endothelial cells (HUVECs) induced apoptosis under the serum-deprived condition. VEGF inhibited apoptosis and augmented the DNA binding of Ets-1 in HUVECs. The inhibition of transcriptional activity of endogenous Ets-1 by a dominant negative molecule intensified the anti-apoptotic effect of VEGF. Caspase inhibitors blocked apoptosis of HUVECs induced by Ets-1. DNA array analysis showed that Ets-1 up-regulated pro-apoptotic genes such as Bid, cytochrome p450, caspase-4, p27, and p21 more than 2 fold, and down-regualted anti-apoptotic genes such as DAD-1, AXL, Cox-2, IAP-2, and MDM-2 less than 0.5 fold in HUVECs. These results indicate that Ets-1 itself is pro-apoptotic to ECs by modulating the expression of apoptosis-related genes. © 2001 Wiley-Liss, Inc. [source] Allicin, the active component of garlic, prevents immune-mediated, concanavalin A-induced hepatic injury in miceLIVER INTERNATIONAL, Issue 3 2005Rafael Bruck Abstract: Background/Aim: Allicin, the immunologically active component of garlic, has been found to affect oxidative stress and immune response in several experimental systems. In the present study, we examined the ability of allicin to prevent immune-mediated, concanavalin A (Con A)-induced liver damage in mice. Methods: Mice were pretreated with allicin for 7 days before their inoculation with Con A (15 mg/kg). The serum levels of liver enzymes and liver histology were examined 24 h after Con A administration. The effect of Con A and allicin on serum levels of tumor necrosis factor-, (TNF-,) and nuclear factor-,B (NF-,B) activation in the liver were examined 2 h after Con A administration, in a separate group of rats, and the effect of allicin on Con A-induced expression of inducible nitric oxide synthase (iNOS) was determined by western blot analysis 24 h after Con A injection. Results: The histopathologic damage in the mouse livers, and the Con A-induced increase of aminotransferases and TNF-, were markedly inhibited in the mice pretreated with allicin before Con A injection (P<0.01). NF-,B binding activity to the nucleus, which increased 2 h after Con A administration, was attenuated by allicin. The expression of iNOS protein which was induced following Con A administration was significantly attenuated by allicin. In vitro studies showed that allicin inhibited TNF-,-mediated T cell adhesion to extracellular matrix components and to endothelial cells. Allicin also inhibited TNF-,-mediated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on human vascular endothelial cells. Conclusions: This study demonstrates that immune-mediated liver damage in mice can be prevented by allicin, probably because of its immunomodulatory effects on T cells and adhesion molecules and inhibition of NF-,B activation. [source] Statins suppress interleukin-6-induced monocyte chemo-attractant protein-1 by inhibiting Janus kinase/signal transducers and activators of transcription pathways in human vascular endothelial cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2010Michihisa Jougasaki Background and purpose:, The mechanisms of anti-inflammatory actions of statins, 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, remain unclear. We investigated the effects of statins on interleukin (IL)-6-induced monocyte chemo-attractant protein (MCP)-1 expression and monocyte chemotaxis. Experimental approach:, Cultures of human aortic endothelial cells (HAECs) were stimulated with IL-6 in the absence and presence of statins. Gene expression and protein secretion of MCP-1, phosphorylation of Janus kinase (JAK) and the signal transducers and activators of transcription (STAT) pathway, and human monocyte migration were examined. Key results:, IL-6 plus its soluble receptor sIL-6R (IL-6/sIL-6R) promoted THP-1 monocyte migration, and increased gene expression and protein secretion of MCP-1, more than IL-6 alone or sIL-6R alone. Various statins inhibited IL-6/sIL-6R-promoted monocyte migration and MCP-1 expression in HAECs. Co-incubation of mevalonate and geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, reversed the inhibitory effects of statins on MCP-1 expression. Geranylgeranyl transferase inhibitor, but not farnesyl transferase inhibitor, suppressed IL-6/sIL-6R-stimulated MCP-1 expression. IL-6/sIL-6R rapidly phosphorylated JAK1, JAK2, TYK2, STAT1 and STAT3, which were inhibited by statins. Transfection of STAT3 small interfering RNA (siRNA), but not STAT1 siRNA, attenuated the ability of IL-6/sIL-6R to enhance THP-1 monocyte migration. In addition, statins blocked IL-6/sIL-6R-induced translocation of STAT3 to the nucleus. Conclusions and implications:, Statins suppressed IL-6/sIL-6R-induced monocyte chemotaxis and MCP-1 expression in HAECs by inhibiting JAK/STAT signalling cascades, explaining why statins have anti-inflammatory properties beyond cholesterol reduction. [source] Interactions between vitreous-derived cells and vascular endothelial cells in vitreoretinal diseasesACTA OPHTHALMOLOGICA, Issue 5 2010Naoki Tojo Abstract. Purpose:, This study aimed to investigate the roles played by vitreous-derived cells in the pathogenesis of vitreoretinal vascular diseases. Methods:, The vitreous was removed from porcine eyes and small pieces were cultured from which vitreous-derived cells were isolated. Polymerase chain reaction and ELISA were performed to determine the expression of vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) at the mRNA and protein levels, respectively. The viability of human retinal endothelial cells (HRECs) exposed to vitreous-derived cells was assessed by MTT assay. Results:, Expression of the mRNA and protein of VEGF and IL-6 was increased by exposing the porcine vitreous-derived cells (PVDCs) to interleukin-1, (IL-1,), interleukin-1, (IL-1,) and tumour necrosis factor , (TNF,), but not to VEGF or IL-6. The percentage of living human vascular endothelial cells was increased by including VEGF and IL-6 in the culture media. The viability of HRECs was affected by co-culturing them with PVDCs that had been exposed to IL-1,, IL-1,, IL-6, TNF, and VEGF. Conclusions:, Porcine vitreous-derived cells are stimulated by IL-1,, IL-1, and TNF,, and produce VEGF and IL-6, which then enhance the proliferation of vascular endothelial cells. This network, including the cytokines and different types of cells, may contribute to the pathogenesis of proliferative vitreoretinal diseases. [source] | ||||||||||