Interleukin-1 alpha mediates an alternative pathway for the antiproliferative action of poly(I.C) on human endothelial cells

• Published in: The Journal of biological chemistry Vol. 267; no. 34; pp. 24375 - 24378
• Main Authors: GARFINKEL, S, HAINES, D. S, BROWN, S, WESSENDORF, J, GILLESPIE, D. H, MACIAG, T
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 05-12-1992
• Subjects: Base Sequence; Biological and medical sciences; Cell cycle, cell proliferation; Cell Division - drug effects; Cell physiology; Cells, Cultured; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Humans; Interferon-beta - biosynthesis; Interferon-beta - genetics; Interleukin-1 - biosynthesis; Interleukin-1 - genetics; Interleukin-1 - physiology; Kinetics; Molecular and cellular biology; Molecular Sequence Data; Oligonucleotides, Antisense - pharmacology; Poly I-C - pharmacology; Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Umbilical Veins; Human; Cell proliferation; Endothelial cell; Double stranded RNA; Transcription; Blood vessel; Interleukin 1; Inhibition
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)35776-4

The antiproliferative effect of double-stranded RNA (dsRNA) on human tumor and normal cells has been well established. However,
the genes involved in the dsRNA-induced antiproliferative response and the molecular mechanisms by which this occurs remain
less well defined. We have studied the ability of synthetic dsRNA, polyinosinic:polycytidylic acid (poly(I.C)) to modify human
umbilical vein endothelial cell (HUVEC) growth and report that poly(I.C) induces a dose-dependent inhibition of HUVEC proliferation
in vitro. In addition, the mRNA levels for the cytokines interleukin-1 alpha (IL-1 alpha) and interferon-beta 1 are induced
in poly(I.C)-treated cells. Moreover, the growth inhibitory effects of poly(I.C) are relieved when cells are grown in the
presence of an IL-1 alpha antisense oligonucleotide to the human IL-1 alpha transcript. Thus, the effects of poly(I.C) appear
to be mediated, in part, through the function of IL-1 alpha, suggesting an alternative pathway for dsRNA-mediated inhibition
of human endothelial cell growth.