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IL-1β down-regulates ADAMTS-13 mRNA expression in cells of the central nervous system

G Alkistis Frentzou1, Claire Bradford, Kirsty A Harkness

  • 1Biomedical Research Centre, Faculty of Health and Wellbeing, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK. g.a.frentzou@leeds.ac.uk

Journal of Molecular Neuroscience : MN
|July 7, 2011
PubMed

Insights

ADAMTS-13, a protease regulating blood clotting, is expressed in brain cells. Interleukin-1β reduces its expression in some brain cells, suggesting a role in local inflammation and hemostasis.

Area of Science:

  • Neuroscience
  • Hematology
  • Molecular Biology

Background:

  • ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) cleaves Von Willebrand factor (vWF) multimers, preventing thrombosis.
  • Reduced ADAMTS-13 activity is linked to thrombotic microangiopathies.
  • The expression and regulation of ADAMTS-13 in the central nervous system (CNS) are not well understood.

Purpose of the Study:

  • To investigate the cellular origin and regulation of ADAMTS-13 expression within the CNS.
  • To determine if inflammatory cytokines affect ADAMTS-13 expression in CNS-derived cell lines.

Main Methods:

  • Analysis of ADAMTS-13 mRNA and protein expression in four human CNS cell lines (neuroblastoma, astroglioma, microglia, and brain endothelial cells).
  • Treatment of cell lines with inflammatory cytokines: Interleukin (IL)-1β, Tumor Necrosis Factor (TNF), and IL-6.
  • Quantitative assessment of changes in ADAMTS-13 expression levels.

Main Results:

  • All tested CNS cell lines constitutively expressed ADAMTS-13 mRNA, with neuroblastoma cells showing the highest levels.
  • IL-1β significantly down-regulated ADAMTS-13 mRNA expression in astroglioma and microglial cells.
  • IL-1β reduced ADAMTS-13 protein levels in astroglioma cells in a dose-dependent manner.

Conclusions:

  • This study is the first to report ADAMTS-13 expression in CNS-derived cells.
  • IL-1β's ability to reduce ADAMTS-13 in microglia and astroglioma cells suggests a potential role in local CNS hemostasis during inflammation.
  • The precise function of ADAMTS-13 within the brain requires further investigation.

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