Effects of OX40-OX40 ligand interaction on the levels of ROS and Cyclophilin A in C57BL/6J mice atherogenesis.

Abstract

BACKGROUND:

An increasing amount of evidence shows that the OX40-OX40L interaction serves an important function in atherosclerosis. However, the mechanism of the OX40 signaling pathway remains unclear. This study investigates the effect of OX40-OX40L interaction on the levels of intracellular reactive oxygen species (ROS) and the secretion of Cyclophilin A (CyPA) in C57BL/6J mice atherogenesis.

METHODS:

The atherosclerotic plaque model was established by placing a rapid perivascular carotid collar on C57BL/6J mice fed with a western-type diet. In vivo, the expressions of CyPA in mouse plaque and lymphocytes were detected by immunohistochemical and Western blot analyses, respectively. In vitro, the expression of CyPA protein in cultured lymphocytes of C57BL/6J mice was assessed by using Western blot analysis. The level of ROS was detected through flow cytometry.

RESULTS:

CyPA expression was significantly increased in the atherosclerotic lesions and lymphocytes from C57BL/6J mice. The ROS levels in OX40(+)-lymphocytes were increased in vitro and in vivo. After stimulating the OX40-OX40L interaction, the ROS and CyPA levels in lymphocytes were obviously increased in vitro, whereas anti-OX40L mAb significantly down-regulated the anti-OX40 mAb-induced ROS generation and inhibited CyPA secretion in lymphocytes.

CONCLUSION:

The OX40-OX40L interaction up-regulates intracellular levels of ROS in C57BL/6J mice and increases CyPA secretion in lymphocytes. Increased CyPA secretion may serve an important function in atherosclerotic plaque formation.

• Authors: Jinchuan Yan, Ying Li, Zhongqun Wang, Yi Liang, Wei Yuan, Cuiping Wang
• Journal: International journal of cardiology (Int J Cardiol) Vol. 176 Issue 2 Pg. 405-12 (Sep 20 2014) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 25115246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• OX40 Ligand
• Reactive Oxygen Species
• Receptors, OX40
• Tnfrsf4 protein, mouse
• Cyclophilin A

Topics

• Animals
• Atherosclerosis (metabolism, pathology)
• Cells, Cultured
• Cyclophilin A (biosynthesis, metabolism)
• Lymphocytes (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• OX40 Ligand (biosynthesis)
• Protein Binding (physiology)
• Reactive Oxygen Species (metabolism)
• Receptors, OX40 (biosynthesis)