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Activation of PPARbeta/delta inhibits leukocyte recruitment, cell adhesion molecule expression, and chemokine release

Laura Piqueras1, Maria Jesus Sanz, Mauro Perretti

  • 1Fundacion Hospital Clinico Universitario de Valencia, Universidad de Valencia, Valencia, Spain.

Journal of Leukocyte Biology
|April 25, 2009
PubMed

Insights

Activation of the nuclear receptor PPARbeta/delta inhibits tumor necrosis factor-alpha-induced neutrophil recruitment and adhesion molecule expression. This finding highlights PPARbeta/delta

Area of Science:

  • Immunology
  • Molecular Biology
  • Vascular Biology

Background:

  • Neutrophil infiltration into tissues is a hallmark of inflammation, driven by chemotactic mediators and endothelial cell adhesion molecule (CAM) expression.
  • The nuclear receptor PPARbeta/delta is present in vascular endothelium, but its role in acute inflammation is not well understood.

Purpose of the Study:

  • To investigate the role of PPARbeta/delta in modulating acute inflammation, specifically neutrophil recruitment and endothelial cell interactions.

Main Methods:

  • Intravital microscopy in mouse cremasteric microcirculation to observe leukocyte rolling, adhesion, and emigration.
  • In vitro studies using human umbilical vein endothelial cells (HUVECs) under physiological flow conditions.
  • Analysis of adhesion molecule expression (ICAM-1, VCAM-1, E-selectin) and chemokine release (GRO-alpha).

Main Results:

  • Activation of PPARbeta/delta with GW501516 significantly inhibited TNF-alpha-induced leukocyte rolling, adhesion, and emigration in vivo.
  • GW501516 reduced the expression of ICAM-1, VCAM-1, and E-selectin on endothelial cells.
  • In vitro, GW501516 markedly inhibited rolling and adhesion of human neutrophils on activated HUVECs, reducing chemokine release and adhesion molecule mRNA expression.

Conclusions:

  • PPARbeta/delta activation effectively modulates acute inflammation by targeting neutrophil-endothelial cell interactions.
  • The findings suggest PPARbeta/delta is a potential therapeutic target for inflammatory conditions.

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