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Cytotoxicity of cytokines in cerebral microvascular endothelial cell

Hitoshi Kimura1, Ilker Gules, Toshinari Meguro

  • 1Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS 39216, USA.

Brain Research
|October 22, 2003
PubMed

Insights

Tumor necrosis factor-alpha (TNF-alpha) induces apoptosis in brain endothelial cells via caspase-3. Interleukin-1 beta (IL-1beta) also causes cell death but through a different pathway, highlighting distinct cytokine roles in cerebral injury.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Elevated levels of pro-inflammatory cytokines, including TNF-alpha, IL-1beta, IL-6, and IL-8, are observed in cerebrospinal fluid (CSF) post-subarachnoid hemorrhage (SAH).
  • These cytokines may play a role in the pathogenesis of cerebral vasospasm and ischemia following SAH.

Purpose of the Study:

  • To investigate the cytotoxic effects of TNF-alpha, IL-1beta, IL-6, and IL-8 on cultured human cerebral microvascular endothelial cells.
  • To elucidate the specific mechanisms by which these cytokines induce cell death.

Main Methods:

  • Cell viability assays were performed to assess cell survival.
  • DNA fragmentation analysis (DNA laddering) was used to detect apoptosis.
  • Western blot analysis for Poly(ADP-ribose) polymerase (PARP) cleavage and caspase-3 activity assays were conducted.

Main Results:

  • TNF-alpha and IL-1beta, but not IL-6 or IL-8, induced dose-dependent cell detachment.
  • Both TNF-alpha and IL-1beta triggered DNA fragmentation.
  • TNF-alpha, but not IL-1beta, cleaved PARP and increased caspase-3 activity, which was inhibited by a caspase-3 inhibitor.

Conclusions:

  • TNF-alpha induces apoptosis in cerebral endothelial cells through caspase-3 activation and PARP cleavage.
  • IL-1beta induces cell death and DNA fragmentation but via a pathway independent of PARP cleavage and caspase-3 activation.
  • These findings suggest distinct apoptotic mechanisms for TNF-alpha and IL-1beta in cerebral endothelial cells following SAH.
Abstract

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