Porcine Aortic Endothelial Cell Genes Responsive to Selected Inflammatory Stimulators

Abstract

Use of porcine tissues has been suggested as a promising solution for severe shortage of transplantable human organs. The immediate hurdle for xenotransplantation is acute immune/inflammatory vascular rejection of the transplant. Because endothelial cells play a key role in the initiation and the amplification of inflammation, alteration of gene expression in human endothelial cells, by various inflammatory stimulators has been studied extensively. However, transcriptional changes induced by human and other inflammatory stimulators in porcine endothelial cells have thus far not been Studied. In this study, we treated porcine endothelial cells with human tumor necrosis factor (TNF)-alpha, porcine interferon (IFN)-gamma, H(2)O(2) and lypopolysaccharide (LPS) and profiled transcriptional change at I hr, 6 hr and 24 hr, using pig oligonucleotide 13K microarray. We found that mRNA Species Such as chemokine (C-X-C motif) ligand 6 (CXCL6) and Cathepsin S were significantly induced in porcine endothelial cells, as was previously reported with human endothelial cell. We also found that mRNA species including secreted frizzled-related protein 2 (SFRP2), radical S-adenosyl methionine domain containing 2 (RSAD2). structure specific recognition protein 1 (SSRP1) also were highly overexpressed in porcine endothelial cells. This result shows clues to understand underlying mechanisms of xenotransplantation rejection and the highly responsive porcine genes may serve as novel targets to be regulated for improving the function of grafted porcine donor organs.