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Science 28 September 1990:
Vol. 249. no. 4976, pp. 1570 - 1574
DOI: 10.1126/science.2218499
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Articles

Science, Vol 249, Issue 4976, 1570-1574
Copyright © 1990 by American Association for the Advancement of Science

articles

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

JA Maier, P Voulalas, D Roeder, and T Maciag

Laboratory of Molecular Biology, Jerome H. Holland, Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD 20855.

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. Senescent human endothelial cells were shown to contain high amounts of the transcript for the cytokine interleukin-1 alpha (IL-1 alpha), a potent inhibitor of endothelial cell proliferation in vitro. In contrast, transformed human endothelial cells did not contain detectable IL-1 alpha messenger RNA. Treatment of human endothelial cell populations with an antisense oligodeoxynucleotide to the human IL-1 alpha transcript prevented cell senescence and extended the proliferative life-span of the cells in vitro. Removal of the IL-1 alpha 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-1 alpha.


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