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.

Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

“…Endothelial cells are the target of inflammatory responses and thereby, of a number of severe disorders, including sepsis and multiple organ dysfunctions that occur via LPS stimulation (11). In this study, we detected the expression of the adhesion molecules, E-selectin and ICAM-1 in LPS-treated porcine iliac artery endothelial cells (PIECs), since the upregulation of adhesion molecules and the increased secretion of cytokines and chemokines are known to occur during endothelial cell activation (12)(13)(14).…”

“…Endothelial cells are the target of inflammatory responses and thereby, of a number of severe disorders, including sepsis and multiple organ dysfunctions that occur via LPS stimulation (11). In this study, we detected the expression of the adhesion molecules, E-selectin and ICAM-1 in LPS-treated porcine iliac artery endothelial cells (PIECs), since the upregulation of adhesion molecules and the increased secretion of cytokines and chemokines are known to occur during endothelial cell activation (12)(13)(14).The evolutionary conserved family of mitogen-activated protein kinases (MAPKs) includes extracellular p38 MAPK, extracellular regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) (15). Numerous environmental stresses, such as osmotic shock, ultraviolet irradiation, as well as LPS and pro-inflammatory cytokines, have been confirmed to activate MAPK signaling cascades in a variety of cell lines (11,16).…”

Tumor Necrosis Factor-Alpha Up-Regulates ICAM-1 Expression and Release in Intestinal Myofibroblasts by Redox-Dependent and -Independent Mechanisms

“…Pro-inflammatory mediators, cytokines, and radical oxygen species (ROS) up-regulate the expression of ICAM-1 [Roebuck and Finnegan, 1999;Ying et al, 2009;Angel-Morales et al, 2012;Pina-Canseco Mdel et al, 2012]. In fact, an increased expression of ICAM-1 occurs in different pathological inflammatory conditions, such as psoriasis, atherosclerosis, autoimmune diseases and inflammatory bowel diseases (IBD) [Chatterjee, 1998;Metselaar and Storm, 2005;Van Assche and Rutgeerts, 2005].…”

Anti‐allergic mechanisms of Japanese herbal medicine, yokukansan on mast cells

“…15 Although it is not fully understood how TNF-a triggers vascular damage, induction of cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) by TNF-a is a prerequisite step for inflammatory cell attachment, endothelial cell damage and vascular leakage. [16][17][18][19] Furthermore, another study by Jiang et al 20 showed that oral administration of YKS inhibited the development of atopic dermatitis-like skin lesions in NC/Nga model mice in association with decreased mast cell infiltration. On the basis of these studies, we hypothesized that YKS may affect mast cell/basophil function.…”