Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer

The proliferative potential of human diploid endothelial cells is finite, and cellular senescence in vitro is accompanied by the failure of the endothelial cell to respond to exogenous growth factors. Senescence human endothelial cells were shown to contain high amounts of the transcript for the cytokine interleukin-α (IL-1α) a potent inhibitor of endothelial cell proliferation in vitro. In contrast, tranformed human endothelial cells did not contain detectable IL-α messenger RNA. Treatment of human endothelial cell populations with an antisense oligodeoxynucleotide to the human IL-1α transcript prevented cell senescence and extend the proliferative life-span of the cells in vetro. Removal of the IL-1α antisense oligomer resulted in the generation of the senescent phenotype and loss of proliferative potential. These data suggest that human endothelial cell senescence in vitro is a dynamic process regulated by the potential intracellular activity of IL-1α.
The Number of Cell Divisions that human diploid fibroblasts undergo in vitro is both finite and a function of the number of cumulative population doublings [1]. The lifetime of human [...]