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Biomed Pharmacother. 2019 Jun 11;117:109099. doi: 10.1016/j.biopha.2019.109099. [Epub ahead of print]

15-epi-lipoxin A4 inhibits TNF-α-induced tissue factor expression via the PI3K/AKT/ NF-κB axis in human umbilical vein endothelial cells.

Author information

1
Hematology Department, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, PR China. Electronic address: chenyijian99@163.com.
2
Hematology Department, Affiliated Hospital of Jinggangshan University, Ji'an, 343000, Jiangxi Province, PR China.
3
Hematology Department, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, PR China.
4
Quality Control Department, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, PR China.
5
Hematology Department, Affiliated Hospital of Jinggangshan University, Ji'an, 343000, Jiangxi Province, PR China. Electronic address: commandozjq@tom.com.
6
Quality Control Department, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, PR China. Electronic address: gyfyzlq@163.com.

Abstract

Inflammation and coagulation are two important processes implicated in venous thromboembolism (VTE). 15-epi-lipoxin A4 (15-epi-LXA4) is the epimer of LXA4, a small lipid molecule, is known to play a key role in the resolution of inflammation. This study aimed to demonstrate whether 15-epi-LXA4 could suppress the inflammatory factor tumor necrosis factor-alpha (TNF-α)-induced upregulation of tissue factor (TF), an important regulator of the blood coagulation cascade, and evaluated the possible underlying mechanisms. We found that 15-epi-LXA4 not only reduced the up-regulation of mRNA and antigens, but also lowered the activity of TF (elevated by TNF-α) in primary culture of human umbilical vein endothelial cells (pc-HUVECs). In addition, 15-epi-LXA4 suppressed the activation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, induced by TNF-α, in pc-HUVECs. 15-epi-LXA4 also inhibited the binding of NF-κB on the TF promoter, which is otherwise enhanced by TNF-α. The role of 15-epi-LXA4 in regulating TNF-α-induced effects was enhanced by the PI3K inhibitor and prevented by the PI3K activator. In conclusion, 15-epi-LXA4 lowered the TNF-α-induced high TF expression and activity by suppressing PI3K/AKT signaling activation, thereby reducing the binding capacity of NF-κB on the TF promoter in pc-HUVECs.

KEYWORDS:

15-epi-lipoxin A(4); PI3K/AKT signaling; Tissue factor; Tumor necrosis factor-alpha

PMID:
31200255
DOI:
10.1016/j.biopha.2019.109099
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