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Thrombin regulates CD40 expression in microglial cells

Jonathan R Weinstein1, Russell E Ettinger, Matthew Zhang

  • 1Department of Neurology, School of Medicine, University of Washington, Seattle, Washington 98195, USA. jweinste@u.washington.edu

Neuroreport
|April 18, 2008
PubMed

Insights

Thrombin activates microglial cells, increasing CD40 expression in a dose-dependent manner. This finding suggests a role for thrombin in central nervous system inflammatory diseases like stroke.

Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Biochemistry

Background:

  • Microglial cells are key innate immune cells in the central nervous system.
  • They rapidly respond to injury via proliferation, cytokine release, and antigen expression.
  • Thrombin, a serine proteinase, can activate microglial cells.

Purpose of the Study:

  • To investigate the effect of thrombin on microglial cell activation.
  • To determine the role of thrombin in regulating CD40 expression on microglial cells.

Main Methods:

  • Utilized N9 microglial cells for experiments.
  • Administered pharmaceutical-grade thrombin and measured CD40 expression.
  • Employed thrombin inhibitors, thrombin receptor-activating peptide, and MAPK pathway inhibitors.

Main Results:

  • Thrombin dose-dependently increased CD40 expression in N9 microglial cells.
  • Thrombin inhibition blocked this effect.
  • Thrombin receptor-activating peptide mimicked the effect.
  • Mitogen-activated protein kinase pathway inhibitors modified the response.

Conclusions:

  • Thrombin significantly upregulates CD40 expression on microglial cells.
  • This interaction is mediated through thrombin receptors and MAPK pathways.
  • Thrombin-induced CD40 regulation may contribute to neuroinflammation in conditions like multiple sclerosis and stroke.

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