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

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.(Folia Histochemica et Cytobiologica 2012, Vol.50, No. 3, 407-413)