Protein C activation peptide inhibits the expression of ICAM-1, VCAM-1, and interleukin-8 induced by TNF-α in human dermal microvascular endothelial cells

Folia Histochem Cytobiol. 2012 Oct 8;50(3):407-13. doi: 10.5603/19749.


Activated protein C (APC) is generated from the cleavage of protein C by thrombin coupled to thrombomodulin and, subsequently, is released as protein C activation peptide (papC). The aim of this study was to evaluate the effect of papC on human dermal microvascular endothelial cells (HMEC-1), activated with 5 ng//mL TNF-α. Flow cytometry showed that papC inhibited the expression of VCAM-1 and ICAM-1, after activation with TNF-a. Similarly, RT-PCR analysis revealed that 2 and 4 pM papC inhibited the expression of VCAM-1 and IL-8 mRNA in TNF-α-treated HMEC-1. In addition, the expression of endothelial nitric oxide synthase(eNOS) increased in HMEC-1 treated with papC, compared to those without treatment. Furthermore, Jurkat cell adhesion to HMEC-1 induced by TNF-a was significantly inhibited after the addition of papC, compared to HMEC-1 without papC (p = 0.03). Finally, a control peptide analog to papC showed no effect on the expression of ICAM and VCAM on the surface of HMEC-1. In conclusion, our results suggest that papC exerts anti-inflammatory effects on endothelial cells.

MeSH terms

  • Amino Acid Sequence
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Dermis / blood supply*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Jurkat Cells
  • Microvessels / cytology
  • Molecular Sequence Data
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism*


  • Interleukin-8
  • Oligopeptides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • protein C activator peptide
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide Synthase Type III