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Lipopolysaccharide activation of pericyte's Toll-like receptor-4 regulates co-culture permeability

David A Edelman1, Yang Jiang, James G Tyburski

  • 1Department of Surgery, Wayne State University, 3900 John R, Suite 400 POB, Detroit, MI 48201, USA.

American Journal of Surgery
|May 22, 2007
PubMed
Abstract

Insights

Toll-like receptor-4 (TLR-4) on pericytes regulates capillary permeability. Lipopolysaccharide (LPS) activation of pericyte TLR-4 increases albumin clearance, a process reversed by TLR-4 silencing.

Area of Science:

  • Endothelial and pericyte cell biology
  • Immunology and inflammation

Background:

  • Pericytes (PCs) and microvascular endothelial cells (MVECs) maintain capillary permeability.
  • Pericytes express Toll-like receptor-4 (TLR-4), a key inflammatory mediator.

Purpose of the Study:

  • To investigate the role of lipopolysaccharide (LPS) activation of pericyte TLR-4 in regulating MVEC/PC co-culture permeability.
  • To determine if TLR-4 signaling in pericytes contributes to LPS-induced capillary leak.

Main Methods:

  • Rat pericytes were cultured and transfected with siRNA targeting TLR-4.
  • Western blotting confirmed successful and sustained TLR-4 gene silencing.
  • A co-culture permeability assay measured albumin clearance after LPS treatment.

Main Results:

  • TLR-4 silencing in pericytes was confirmed and lasted for 7 days.
  • LPS induced a dose- and time-dependent increase in albumin clearance in MVEC/PC co-cultures.
  • Eliminating TLR-4 in pericytes abolished the LPS-induced increase in albumin clearance.

Conclusions:

  • TLR-4 signaling in pericytes is a critical regulator of LPS-induced capillary leak.
  • The developed TLR-4 silencing model provides a tool for further research into pericyte-mediated capillary permeability.

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