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

S Garfinkel1, D S Haines, S Brown

  • 1Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855.

The Journal of Biological Chemistry
|December 5, 1992
PubMed

Insights

Synthetic double-stranded RNA (dsRNA) inhibits human endothelial cell growth. This antiproliferative effect is partly mediated by interleukin-1 alpha (IL-1 alpha), revealing a new dsRNA mechanism.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Double-stranded RNA (dsRNA) exhibits antiproliferative effects on various human cells, including tumor and normal cells.
  • The specific genes and molecular mechanisms underlying dsRNA-mediated antiproliferation are not fully elucidated.
  • Human umbilical vein endothelial cells (HUVECs) are crucial for vascular functions and can be influenced by external stimuli.

Purpose of the Study:

  • To investigate the antiproliferative effects of synthetic dsRNA, specifically polyinosinic:polycytidylic acid (poly(I.C)), on HUVEC proliferation.
  • To identify molecular mediators involved in the dsRNA-induced growth inhibition of endothelial cells.
  • To explore potential therapeutic pathways for dsRNA-mediated cellular responses.

Main Methods:

  • Treatment of HUVECs with varying concentrations of poly(I.C) in vitro.
  • Quantification of HUVEC proliferation rates.
  • Measurement of mRNA expression levels for cytokines, including interleukin-1 alpha (IL-1 alpha) and interferon-beta 1.
  • Assessment of poly(I.C)'s inhibitory effects in the presence of an IL-1 alpha antisense oligonucleotide.

Main Results:

  • Poly(I.C) demonstrated a dose-dependent inhibition of HUVEC proliferation in vitro.
  • Treatment with poly(I.C) led to increased mRNA levels of IL-1 alpha and interferon-beta 1 in HUVECs.
  • The antiproliferative effect of poly(I.C) was significantly reduced when cells were co-treated with an IL-1 alpha antisense oligonucleotide.

Conclusions:

  • Synthetic dsRNA, poly(I.C), effectively inhibits human endothelial cell proliferation.
  • Interleukin-1 alpha plays a partial role in mediating the growth inhibitory effects of poly(I.C) on HUVECs.
  • These findings suggest an alternative molecular pathway for dsRNA-induced antiproliferation in human endothelial cells, potentially involving IL-1 alpha signaling.

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