Reduction of Monocyte Chemoattractant Protein‐1 and Interleukin‐8 Levels by Ticlopidine in TNF‐α Stimulated Human Umbilical Vein Endothelial Cells

Abstract

Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1) is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8), a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.

The Protective Effects of a Synthetic Geranyl Acetophenone in a Cellular Model of TNF-α-Induced Pulmonary Epithelial Barrier Dysfunction

“…PCR products for each gene were determined based on the low molecular weight DNA ladder (New England Biolabs, Ipswich, MA, USA). Primers used were adapted from published human gene sequences ( Table 1 ) [ 74 , 75 ]. Band intensities were quantified by Image J Java-based image processing program (NIH, USA), and were normalized by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA.…”

Decreased MicroRNA-221 is Associated with High Levels of TNF-a in Human Adipose Tissue-Derived Mesenchymal Stem Cells From Obese Woman

“…In addition, the plasma levels of pro-inflammatory cytokines like TNF-α [21], interleukin-6 (IL-6) [22] and interleukin-8 (IL-8) [23] are elevated in obese people. TNF- α can stimulate the secretion of inflammatory cytokines such as monocyte chemotactic protein-1 (MCP-1) [24,25] and several adipokines including leptin [26,27] and thrombospondin 1 (TSP1) [28,29]. Serum levels of leptin [30,31] and TSP1 [32] are elevated in obese and insulin-resistant subjects.…”

Comparative Assessment of Transient Exposure of Paclitaxel or Zotarolimus on In Vitro Vascular Cell Death, Proliferation, Migration, and Proinflammatory Biomarker Expression

“…17,18,20 Attenuation by the test article compounds of an artificially induced inflammatory response in cultured HCAECs was evaluated via measurement of cytokine production and mRNA expression. HCAECs were densely seeded (5 · 10 4 cells per centimeter square) in 24-well plates and cultured in EGM-2MV growth media (Lonza), and pretreated for 2 hours with either zotarolimus or paclitaxel over a range of concentrations from 1 pM to 100 nM in EGM-2MV with 0.1% DMSO (n = 6).…”

“…In addition, an established wound-healing endothelial cell (EC) migration assay [14][15][16] with transient exposure to these compounds was used to model and to assess drug effects on cellular functions during reendothelialization. Furthermore, an established in vitro model of induced endothelial inflammation 17,18 was used to assess the effects of these compounds on proinflammatory cytokine production and gene expression. Lastly, a cell death assay focusing on both apoptosis and cytotoxic necrosis was implemented to evaluate trends in EC viability associated with transient exposure to each of these compounds.…”