title: 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.
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-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.
authors.affiliation: CICIMEBIO, Faculty of Medicine and Surgery of Universidad Autonoma Benito Juarez Oaxaca, Oaxaca, Mexico.
authors.forename: María Del Socorro
authors.initials: Mdel S
authors.lastname: Pina-Canseco
authors.forename: Araceli
authors.initials: A
authors.lastname: Páez-Arenas
authors.forename: Felipe
authors.initials: F
authors.lastname: Massó
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pérez-Campos
authors.forename: Ruth
authors.initials: R
authors.lastname: Martínez-Cruz
authors.forename: Pedro
authors.initials: P
authors.lastname: Hernández-Cruz
authors.forename: Abraham
authors.initials: A
authors.lastname: Majluf-Cruz
authors.forename: Margarito
authors.initials: M
authors.lastname: Martínez-Cruz
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez-Campos Mayoral
authors.forename: Alma Dolores
authors.initials: AD
authors.lastname: Pérez-Santiago
authors.forename: Edgar
authors.initials: E
authors.lastname: Zenteno
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D020405:Dermis / Q000098:blood supply*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D055806:Microvessels / Q000166:cytology; D008969:Molecular Sequence Data; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D009842:Oligopeptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C047135:protein C activator peptide; D018799:Intercellular Adhesion Molecule-1; D052250:Nitric Oxide Synthase Type III