earticle

영어

Xenotransplantation has been considered as an alternative to moderate shortage of donor organ for transplantation. To achieve successful xenotransplatation, we need to overcome immune rejection. Even though, hyperacute rejection has been overcome by α1,3-galactosyltransferase knockout pig, cellular immune rejection still remains as a subsequent barrier. Interleukin-10 (IL-10) is known as anti-inflammatory and immunomodulatory cytokine which has been shown to limit inflammatory responses by inhibiting macrophage activation in several animal experiments. To study of effect of human IL-10 (hIL-10) on pig-to-human xenotransplantation, we estabilished porcine kidney epithelial cell line (PK15) expressing hIL-10. When the cells were co-cultured with human monocyte-derived macrophages by phorbol myristate acetate activation, the cytotoxicity of macrophages was decreased by hIL-10. Furthermore, there is a decreased production of pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-23, and increased anti-inflammatory cytokines like IL-10, but not transforming growth factor beta, in the presence of hIL-10. Also, macrophage polarization toward M2-like phenotype were induced by hIL-10 from transgenic PK15 cells. Finally, we found that hIL-10 expressing from porcine cells induces the macrophage polarization into M2-like macrophages, reducing the cytotoxic effect of human macrophages. Therefore, these findings suggest that hIL-10 transgenic pig seems to be considered as an useful model to overcome xenograft rejection.