Downregulation of TNF-αTNF-R1 Signals by AT-Lipoxin A4 May Be a Significant Mechanism of Attenuation in SAP-Associated Lung Injury
Joint Authors
Zhou, Mengtao
Xie, Jianming
Chen, Bi-Cheng
Xiang, Yukai
Dai, Shengjie
Yu, Dinglai
Yu, Suhui
Sun, Hongwei
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-11
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Our previous studies verified the potent anti-inflammatory effects against severe acute pancreatitis (SAP) of AT-Lipoxin A4 and their analogues.
However, the anti-inflammatory effects of AT-Lipoxin A4 on SAP-associated lung injury are not thoroughly known.
We used western blot, polymerase chain reaction (PCR), and immunofluorescence to investigate the downregulation of TNF-α signals in cellular and animal models of SAP-associated lung injury following AT-Lipoxin A4 intervention.
In vitro, we found that AT-Lipoxin A4 markedly suppressed protein expression in TNF-α signals in human pulmonary microvascular endothelial cell, such as tumor necrosis factor receptor-associated factor 2 (TRAF2), TNF-R1-associated death domain (TRADD), receptor-interacting protein (RIP), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin.
Moreover, AT-Lipoxin A4 inhibited downstream signals activated by TNF-α, including NF-κB/p65, JNK/MAPK, and ERK/MAPK.
In vivo, AT-Lipoxin A4 significantly decreased pathological scores of the pancreas and lungs and the serum levels of IL-6 and TNF-α.
Immunofluorescence, western blotting, and real-time PCR assay showed that AT-Lipoxin A4 significantly attenuated the expression of TNF-R1, TRADD, TRAF2, and RIP in the lungs of SAP rats.
In addition, the activation of NF-κB was also downregulated by AT-Lipoxin A4 administration as compared with SAP rats.
AT-Lipoxin A4 could inhibit the production of proinflammatory mediators and activation of TNF-α downstream signals such as NF-κB and MAPK.
Downregulation of TNF-α signals by AT-Lipoxin A4 may be a significant mechanism in the attenuation of SAP-associated lung injury.
American Psychological Association (APA)
Yu, Suhui& Xie, Jianming& Xiang, Yukai& Dai, Shengjie& Yu, Dinglai& Sun, Hongwei…[et al.]. 2019. Downregulation of TNF-αTNF-R1 Signals by AT-Lipoxin A4 May Be a Significant Mechanism of Attenuation in SAP-Associated Lung Injury. Mediators of Inflammation،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1193599
Modern Language Association (MLA)
Yu, Suhui…[et al.]. Downregulation of TNF-αTNF-R1 Signals by AT-Lipoxin A4 May Be a Significant Mechanism of Attenuation in SAP-Associated Lung Injury. Mediators of Inflammation No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1193599
American Medical Association (AMA)
Yu, Suhui& Xie, Jianming& Xiang, Yukai& Dai, Shengjie& Yu, Dinglai& Sun, Hongwei…[et al.]. Downregulation of TNF-αTNF-R1 Signals by AT-Lipoxin A4 May Be a Significant Mechanism of Attenuation in SAP-Associated Lung Injury. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1193599
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1193599