Hypoxia influences CD40-CD40L mediated inflammation in endothelial and monocytic cells.
Publication/Presentation Date
2-21-2009
Abstract
The interaction between CD40 and its ligand (CD40L) has been implicated in the pathogenesis of atherosclerosis and is recognized as a central event in the development of immuno-inflammatory processes. Our previous studies have shown that the CD40-CD40L interaction modulates platelet, neutrophil, and endothelial reactive oxygen species (ROS) generation. Hypoxia, known to be associated with tissue ischemia and inflammation, also influences the ROS production and changes the cellular redox state. However, the effect of hypoxia on CD40-CD40L mediated vascular inflammation is unknown. We have investigated whether hypoxia influences CD40-CD40L mediated vascular inflammatory responses, ROS production, and cellular interactions. We found that hypoxia significantly enhances the inflammatory effect of CD40L in both endothelial and monocytic cells (THP1). CD40-CD40L interaction in the presence of hypoxia induces ROS production, the synthesis of an inflammatory adhesive protein intercellular adhesion molecule 1 (ICAM1) and activates stress response proteins (p38 MAP kinase and HSP27), indicating that CD40L mediates the induction of oxidative stress in these cells. Importantly, we found that the effects of CD40L can be transmitted between HUVECs and monocytic THP1 cells through intercellular CD40-CD40L interaction and these processes are augmented under hypoxia. Together, these data indicate that under hypoxic conditions the CD40-CD40L interaction significantly influences adhesion molecule expression, stress generation, actin polymerization, and monocytic adhesion to endothelial cells in addition to changes in signaling. In summary, we show that hypoxia can alter CD40-CD40L mediated endothelial-monocyte interaction, playing a significant role in vascular inflammation and cellular adhesion processes.
Volume
122
Issue
2
First Page
170
Last Page
184
ISSN
1879-0542
Published In/Presented At
Chakrabarti, S., Rizvi, M., Pathak, D., Kirber, M. T., & Freedman, J. E. (2009). Hypoxia influences CD40-CD40L mediated inflammation in endothelial and monocytic cells. Immunology letters, 122(2), 170–184. https://doi.org/10.1016/j.imlet.2008.12.010
Disciplines
Medicine and Health Sciences
PubMedID
19187784
Department(s)
Department of Medicine, Hematology-Medical Oncology Division
Document Type
Article