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

Abstract

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-a. 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-a-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 antiinflammatory
effects on endothelial cells.