Nucleosomes activate NF-kappaB in endothelial cells for induction of the proangiogenic cytokine IL-8

Int J Cancer. 2004 Oct 20;112(1):155-60. doi: 10.1002/ijc.20390.

Abstract

Solid tumors often exhibit regions undergoing apoptosis and necrosis, also referred to as "aponecrosis", juxtaposed to sites of active angiogenesis. We explored whether nucleosomes resulting from aponecrosis induced the angiogenic factor IL-8 in vascular endothelial cells. Results indicate that nucleosomes induced IL-8. Nucleosomes increased IL-6 and IL-8 mRNA but not IL-10, TNF-alpha, VEGF or FGF-2 mRNA. Induction of IL-8 by nucleosomes in endothelial cells appeared to be the result of NF-kappaB/RelA transcription factor activation. The increased expression of IL-8 in vascular endothelial cells following nucleosome stimulation suggests that aponecrosis could play an important role in the promotion of tumor angiogenesis.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Cells, Cultured
  • Endothelium, Vascular / physiology*
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • NF-kappa B / metabolism*
  • Neovascularization, Physiologic*
  • Nucleosomes / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Umbilical Veins / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Nucleosomes
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Interleukin-10