Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells

Dorothee Viemann1, Anke Strey, Annette Janning

  • 1Institute of Experimental Dermatology, Integrated Functional Genomics, and the Interdisciplinary Clinical Research Center, University Hospital Muenster, University of Muenster, Röntgenstrasse 21, 48149 Muenster, Germany. viemannd@uni-muenster.de

Blood
|December 16, 2004
PubMed

Insights

Myeloid-related proteins (MRP8/MRP14) trigger inflammation and clotting in endothelial cells. These S100 proteins, elevated in vasculitis, may be targets for anti-inflammatory therapies.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Myeloid-related protein 8 (MRP8) and MRP14 are S100 proteins secreted by activated phagocytes.
  • These proteins bind to endothelial cells, but their specific effects on endothelial cells are not well understood.

Purpose of the Study:

  • To investigate the endothelial cell response to MRP8/MRP14.
  • To determine the role of MRP8/MRP14 in inflammatory conditions.

Main Methods:

  • Oligonucleotide microarray analysis was used to assess gene expression changes in human microvascular endothelial cells.
  • Biochemical and functional assays were employed to confirm gene expression findings.
  • MRP8/MRP14 expression levels were correlated with inflammatory activity in systemic vasculitis.

Main Results:

  • MRP8/MRP14 significantly altered gene expression in endothelial cells, promoting a thrombogenic and inflammatory profile.
  • Key changes included increased transcription of pro-inflammatory chemokines and adhesion molecules.
  • Decreased expression of cell junction proteins and molecules maintaining monolayer integrity was observed.
  • MRP8/MRP14 expression correlated with inflammatory activity in systemic vasculitis.

Conclusions:

  • MRP8/MRP14 induce a pro-thrombotic and inflammatory response in endothelial cells.
  • These proteins play a significant role in endothelial inflammatory reactions, particularly in systemic vasculitis.
  • MRP8/MRP14 represent potential novel therapeutic targets for anti-inflammatory strategies.