Kurzfassung

For several years we analyze the pathogenic effects of antiphospholipid antibodies (aPL). We could show that endosomal NADPH oxidase (NOX) is critically involved in aPL mediated signal transduction and the activation of procoagulant and proinflammatory pathways. This does not only involve effects on gene expression but also the translocation of toll like receptors (TLR) from the endoplasmic reticulum (ER) to the endosome. The mechanisms how aPL activate endosomal NOX are a major topic or our...For several years we analyze the pathogenic effects of antiphospholipid antibodies (aPL). We could show that endosomal NADPH oxidase (NOX) is critically involved in aPL mediated signal transduction and the activation of procoagulant and proinflammatory pathways. This does not only involve effects on gene expression but also the translocation of toll like receptors (TLR) from the endoplasmic reticulum (ER) to the endosome. The mechanisms how aPL activate endosomal NOX are a major topic or our research. We assume that the endosomal phospholipid bis(monoacylglycerol)-phosphate (BMP) which is bound by aPL is critically involved in this process. A second relevant question is how endosomal NOX activates cellular processes such as translocation of TLRs. In a first step we want to identify proteins which are oxidatively modified by reactive oxygen species (ROS) after activation of endosomal NOX.
Our preliminary data suggest that endosomal NOX might be an interesting target for pharmacologic interventions. For example, hydroxychloroquine is able to inhibit activation of endosomal NOX not only by aPL but also by cytokines such as TNFα.» weiterlesen» einklappen