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Angiogenesis

, Volume 4, Issue 2, pp 155–162 | Cite as

Vascular endothelial growth factor is upregulated by interleukin-1β in human vascular smooth muscle cells via the P38 mitogen-activated protein kinase pathway

  • Young D. Jung
  • Wenbiao Liu
  • Niels Reinmuth
  • Syed A. Ahmad
  • Fan Fan
  • Gary E. Gallick
  • Lee M. Ellis
Article

Abstract

Small tumor vessels are composed of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). These cells have been shown to communicate with each other via cytokine signaling during neovascularization. We previously demonstrated that interleukin-1β (IL-1β) leads to induction of vascular endothelial growth factor (VEGF) in human colon carcinoma cells. As pericytes play a role in regulating EC function, we hypothesized that IL-1β may mediate EC survival by induction of VEGF in a paracrine manner. We investigated the effects of IL-1β on VEGF expression in human VSMCs (hVSMCs) and the signal transduction pathways that may be involved. Treatment of hVSMCs with IL-1β induced VEGF expression in a time- and concentration-dependent manner and increased both the VEGF promoter activity and the mRNA half-life. Treatment with IL-1β induced the expression of P38 mitogen-activated protein kinase (MAPK) within 5 min but did not activate extracellular signal-regulated kinases (Erk)-1/2, c-jun amino terminal kinase (JNK), or Akt. SB203580, a specific P38 MAPK inhibitor, blocked the ability of IL-1β to induce VEGF mRNA and promoter activity. Conditioned media from hVSMCs pretreated with IL-1β prevented apoptosis of ECs, an effect that was partially abrogated by VEGF-neutralizing antibodies. These data demonstrate that IL-1β may induce VEGF in hVSMCs, and suggest that this paracrine signaling pathway, may prevent, in part, apoptosis of ECs.

angiogenesis IL-1β signal transduction VEGF VSMC 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Young D. Jung
    • 1
  • Wenbiao Liu
    • 1
  • Niels Reinmuth
    • 1
  • Syed A. Ahmad
    • 2
  • Fan Fan
    • 1
  • Gary E. Gallick
    • 1
  • Lee M. Ellis
    • 1
    • 3
  1. 1.Department of Cancer BiologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Surgical OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of Surgical OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA Tel:

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