: Transplant patients are currently subjected to long term morbid therapy with immunosuppressive medications in order to prevent rejection of their grafts. For this reason, it is critical to devise therapies that are more specific and have improved side effect profiles. This will require a greater understanding into the mechanisms of allograft rejection. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor known. An underappreciated biologic function of VEGF is its role in initiating and perpetuating an inflammatory response through the induction of proinflammatory chemokines. Furthermore, this function of VEGF has major implications for alloimmune recognition. This proposal seeks to elucidate the mechanisms by VEGF can exert an inflammatory response in the setting of alloimmune stimulation. The understanding gained through these experiments is likely to uncover new, more specific targets for the treatment of allograft rejection. ? ?
| Flaxenburg, Jesse A; Melter, Michael; Lapchak, Peter H et al. (2004) The CD40-induced signaling pathway in endothelial cells resulting in the overexpression of vascular endothelial growth factor involves Ras and phosphatidylinositol 3-kinase. J Immunol 172:7503-9 |
