Inflammatory Interaction Between LIGHT and ProteinaseActivated Receptor-2 in Endothelial Cells by Wiggo J. Sandberg, Bente Halvorsen, Arne Yndestad, Camilla Smith, Kari Otterdal, Frank R. Brosstad, Stig S. Frøland, Peder S. Olofsson, Jan K. Damås, Lars Gullestad, Göran K. Hansson, Erik Øie, and Pål Aukrust Circulation Research Volume 104(1):60-68 January 2, 2009 Copyright © American Heart Association, Inc. All rights reserved. Figure 1. LIGHT induces PAR-2 expression in endothelial cells. Wiggo J. Sandberg et al. Circ Res. 2009;104:60-68 Copyright © American Heart Association, Inc. All rights reserved. Figure 2. PAR-2 signaling enhances LIGHT-mediated chemokine release from HUVECs. Cells were incubated with the PAR-2–activating peptide SLIGKV (10 μmol/L and 100 μmol/L), rhLIGHT (100 ng/mL), or a combination thereof. Wiggo J. Sandberg et al. Circ Res. 2009;104:60-68 Copyright © American Heart Association, Inc. All rights reserved. Figure 3. The LIGHT-induced upregulation of PAR-2 in HUVECs is mediated through HVEM. Transfected cells with silencing RNA for both LIGHT receptors, LTβR and HVEM, were incubated with rhLIGHT (100 ng/mL) for 5 hours, and PAR-2 mRNA levels were measured by real-time quantitative RT-PCR and normalized to β-actin expression. Wiggo J. Sandberg et al. Circ Res. 2009;104:60-68 Copyright © American Heart Association, Inc. All rights reserved. Figure 4. LIGHT-mediated PAR-2 expression in HUVECs involves activation of JNK and NF-κB intracellular pathways. Wiggo J. Sandberg et al. Circ Res. 2009;104:60-68 Copyright © American Heart Association, Inc. All rights reserved. Figure 5. LIGHT induces PAR-2 expression in human monocytes. Wiggo J. Sandberg et al. Circ Res. 2009;104:60-68 Copyright © American Heart Association, Inc. All rights reserved. Figure 6. Representative photomicrographs demonstrating LIGHT, HVEM, LTβR, and PAR-2 immunostaining within (middle images) and outside (left images) the atherosclerotic lesions of aorta in a 18-week-old atherosclerotic ApoE−/− mouse and in the aorta of a C57BL/6 nonatherosclerotic control mouse (right images). Wiggo J. Sandberg et al. Circ Res. 2009;104:60-68 Copyright © American Heart Association, Inc. All rights reserved. Figure 7. Enhanced expression of PAR-2, LIGHT, LTβR, and HVEM in the aorta of ApoE−/− mice. Wiggo J. Sandberg et al. Circ Res. 2009;104:60-68 Copyright © American Heart Association, Inc. All rights reserved. Figure 8. Increased PAR-2 expression in monocytes from unstable angina patients. Wiggo J. Sandberg et al. Circ Res. 2009;104:60-68 Copyright © American Heart Association, Inc. All rights reserved.
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