Programmed Cell Death Protein 2-like Promotes Inflammation and Oxidative Stress in Vascular Endothelial Cells.

Abstract

Programmed cell death protein 2-like (PDCD2L) is a shuttle protein of the nucleus and cytoplasm and is related to the ribosome biogenesis. However, there are few reports on the relationship between PDCD2L and inflammation, and the exact relationship between PDCD2L and inflammation has not been determined in vascular endothelial cells yet. Accordingly, we focus on exploring the relationship between PDCD2L and inflammation and its potential mechanisms. Our research findings suggested that PDCD2L is a proinflammatory target. The result showed that, by interfering with the expression of PDCD2L, LPS-induced inflammation of vascular endothelial cells can be reduced, such as IL-6 and IL-1β, as well as the adhesion factor ICAM1. Meanwhile, overexpression of PDCD2L can further increase LPS-induced inflammation levels, ICAM1, and ROS production, reduce CAT, GSH/GSSG levels, and increase SOD levels. Therefore, we determined that PDCD2L has a regulatory effect on inflammation and oxidative stress of vascular endothelial cells, and its regulatory mechanism may be related to inflammatory transcription factors STAT1, NF-κB regulation, transport of inflammatory messenger mRNA, and ribosome biogenesis. Then, we screened that andrographolide (Andro) can bind to PDCD2L, thus inhibiting inflammation and endothelial cell adhesion caused by the overexpression of PDCD2L. This study reveals that PDCD2L is a potential anti-inflammatory therapeutic target, providing new exploration for the development of anti-inflammatory drugs.

• Authors: Caifeng Li, Zhao Cui, Shiwen Deng, Tong Lei, Peng Chen, Hongjun Yang
• Journal: ACS pharmacology & translational science (ACS Pharmacol Transl Sci) Vol. 6 Issue 10 Pg. 1453-1470 (Oct 13 2023) ISSN: 2575-9108 [Electronic] United States
• PMID: 37854614 (Publication Type: Journal Article)
• Copyright: © 2023 American Chemical Society.