Interleukin-13 protects endothelial cells from apoptosis and activation - Association with the protective genes A20 and A1

Background Chronic rejection is the major obstacle to long-term survival of allografts and is associated with graft endothelial cell activation and ap optosis. Recent reports have found an association between graft survival, p resence of Th2 cytokines, and expression by endothelial cells of cytoplasmi c "protective" molecules that prevent apoptosis and down-regulate the infla mmatory process. Methods. Cultured human umbilical vein endothelial cells (HUVEC) were used. Apoptotic cells were detected by staining with FITC-annexinV followed by f low cytometry. Expression of vascular cell adhesion molecule-1, E-selectin, and intercellular adhesion molecule-l were also measured by flow cytometry . Transcripts were detected by reverse transcription-PCR and quantitation w as achieved by co-amplification of competing, internal standard RNA. Results. We demonstrate that exposure of HUVEC to interleukin (IL)-13 for 7 2 hr afforded partial protection from apoptosis induced by tumor necrosis f actor-alpha/cycloheximide or serum starvation. Pretreatment with IL-13 also modulated induction of E-selectin after acute exposure to tumor necrosis f actor-alpha or IL-1 alpha. Protection was associated with transcription of the genes Al and A20. Prolonged treatment with IL-13 had minimal proinflamm atory effects and did not induce expression of E-selectin or vascular cell adhesion molecule-1 or increase intercellular adhesion molecule-1 above bas al levels. Conclusions. Our data provide a possible explanation for the observed assoc iation between Th2 cytokines and expression of protective genes in the endo thelium of long-surviving allografts and xenografts.