| Autor: |
Yijian Chen, Yongliang Zheng, Liuyan Xin, Sisi Zhong, Aifei Liu, Wenhong Lai, Liping Liu, Chuanming Lin, Changfeng Liao, Junquan Zeng, Liqun Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Biomedicine & Pharmacotherapy, Vol 117, Iss , Pp - (2019) |
| Druh dokumentu: |
article |
| ISSN: |
0753-3322 |
| DOI: |
10.1016/j.biopha.2019.109099 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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