Egbert K. O. Kruithof
University of Geneva
Endothelial stem cellInternal medicineEndocrinologyAntigenMolecular biologyAntibodyReceptorChemistryImmunologyPlasminogen activator inhibitor-2FibrinolysisUrokinasePlasminogen activatorPlasminogen activator inhibitor-1T-plasminogen activatorFibrinBiochemistryMedicineCell cultureBiologyCell biology
94Publications
41H-index
5,338Citations
Publications 99
Newest
Last. Karim J. BrandtH-Index: 12
view all 6 authors...
Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of so-called antiphospholipid antibodies and clinical manifestations such as recurrent thromboembolic or pregnancy complications. Although the main antigenic determinant for antiphospholipid antibodies has been identified as the β-2-glycoprotein 1 (β2GP1), the precise epitope recognized by antiphospholipid antibodies still remains largely unknown. In the study herein, we wanted to identify a sequence in dom...
8 CitationsSource
The characteristic hemorrhages of acute promyelocytic leukemia (APL) are caused in part by the high expression of tissue factor (TF) on leukemic cells, which also produce TNF and IL-1β, proinflammatory cytokines known to increase TF in various cell types. Exposure of NB4 cells, an APL cell line, to all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) rapidly and strongly reduced TF mRNA. Both drugs also reduced TNF mRNA, but later, and moreover increased IL-1β mRNA. The effect on procoagulan...
8 CitationsSource
#1Martina Barnevik Olsson (University of Gothenburg)H-Index: 8
#2Karin Hultman (Lund University)H-Index: 11
Last. Christina Jern (University of Gothenburg)H-Index: 43
view all 7 authors...
The serine protease tissue-type plasminogen activator (t-PA) is involved in both vital physiological brain processes, such as synaptic plasticity, and pathophysiological conditions, such as neurodegeneration and ischemic stroke. Recent data suggest that epigenetic mechanisms play an important role in the regulation of t-PA in human endothelial cells. However, there are limited data on epigenetic regulation of t-PA in human brain-derived cells. We demonstrate that treatment of cultured human neur...
2 CitationsSource
#1Sylvie Dunoyer-Geindre (University of Geneva)H-Index: 16
#2Anne-Sophie Rivier-Cordey (University of Geneva)H-Index: 4
Last. Egbert K. O. Kruithof (University of Geneva)H-Index: 41
view all 5 authors...
: Expression of the tissue-type plasminogen activator gene (t-PA; gene name PLAT) is regulated, in part, by epigenetic mechanisms. We investigated the relationship between PLAT methylation and PLAT expression in five primary human cell types and six transformed cell lines. CpG methylation was analyzed in the proximal PLAT gene promoter and near the multihormone responsive enhancer (MHRE) -7.3 kilobase pairs upstream of the PLAT transcriptional start site (TSS, -7.3 kb). In Bowes melanoma cells, ...
6 CitationsSource
The antiphospholipid antibody syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). We recently demonstrated that Toll-like receptor 2 (TLR2) and CD14 contribute to monocyte activation of aPLA.
35 CitationsSource
#1Egbert K. O. Kruithof (University of Geneva)H-Index: 41
#2Sylvie Dunoyer-Geindre (University of Geneva)H-Index: 16
Tissue-type plasminogen activator (t-PA ) plays an important role in the removal of intravascular fibrin deposits and has several physiological roles and pathological activities in the brain. Its production by many other cell types suggests that t-PA has additional functions outside the vascular and central nervous system. Activity of t-PA is regulated at the level of its gene transcription, its mRNA stability and translation, its storage and regulated release, its interaction with cofactors tha...
36 CitationsSource
#1Karim J. BrandtH-Index: 12
Last. Philippe de MoerlooseH-Index: 44
view all 4 authors...
Localization of Toll-like receptors (TLR) in subcellular organelles is a major strategy to regulate innate immune responses. While TLR4, a cell-surface receptor, signals from both the plasma membrane and endosomal compartments, less is known about the functional role of endosomal trafficking upon TLR2 signaling. Here we show that the bacterial TLR2 ligands Pam3CSK4 and LTA activate NF-κB-dependent signaling from endosomal compartments in human monocytes and in a NF-κB sensitive reporter cell lin...
46 CitationsSource
#1Karim J. BrandtH-Index: 12
Last. Philippe de MoerlooseH-Index: 44
view all 3 authors...
Abstract The antiphospholipid syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). The plasma protein β2-glycoprotein 1 (β2GP1) has been identified as a major target of aPLA associated with APS. Cell activation by aPLA appears to be a major pathogenic cause in the pathogenesis of APS. Receptors, co-receptors and accessory molecules are known to assist the pathogenic effect...
27 CitationsSource
#1Nathalie SattaH-Index: 15
Last. Philippe de MoerlooseH-Index: 44
view all 8 authors...
The presence of antiphospholipid antibodies (aPLAs) is associated with arterial or venous thrombosis and/or recurrent fetal loss. The proposed pathogenic mechanisms for aPLA effects include the inflammatory activation of monocytes and endothelial cells. Toll-like receptors (TLRs) are candidate signaling intermediates. The aim of this study was to investigate the relative contribution of TLR2 and TLR4 in cell activation by aPLAs. Of 32 patient-derived aPLAs, 19 induced an inflammatory activation ...
84 CitationsSource
#1Sylvie Dunoyer-Geindre (Geneva College)H-Index: 16
#2Egbert K. O. Kruithof (Geneva College)H-Index: 41
Aims Tissue-type plasminogen activator (t-PA) is produced by endothelial cells (EC) and is responsible for the removal of intravascular fibrin deposits. We investigated whether expression of t-PA by EC is under epigenetic control. Methods and results Methylation analysis of the proximal t-PA promoter revealed a stretch of unmethylated CpG dinucleotides from pos- ition 2121 to +59, while upstream CpG dinucleotides were all methylated. In contrast, in human primary hepato- cytes, which express t-P...
28 CitationsSource