Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway
Joint Authors
Zhou, Mengtao
Chen, Bi-Cheng
Zhang, Fan
Shi, Ke-Qing
Zheng, Chenlei
Ni, Xiao-feng
Xiang, Yukai
Yu, Dinglai
Ye, Wen
Pan, Reguang
Shi, Zhehao
Zhang, Zhongjing
Zhang, Qiyu
Sun, Hongwei
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-06
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Acute lung injury (ALI) is a critical event involved in the pathophysiological process of acute pancreatitis (AP).
Many methods have been widely used for the treatment of AP-ALI, but few are useful during early inflammation.
Lipoxin A4 (LXA4), a potent available anti-inflammatory and novel antioxidant mediator, has been extensively studied in AP-ALI, but its underlying mechanism as a protective mediator is not clear.
This research was conducted to identify the possible targets and mechanisms involved in the anti-AP-ALI effect of LXA4.
First, we confirmed that LXA4 strongly inhibited AP-ALI in mice.
Next, using ELISA, PCR, and fluorescence detection to evaluate different parameters, LXA4 was shown to reduce the inflammatory cytokine production induced by AP and block reactive oxygen species (ROS) generation in vivo and in vitro.
In addition, TNF-α treatment activated the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream gene heme oxygenase-1 (HO-1) in human pulmonary microvascular endothelial cells (HPMECs), and LXA4 further promoted their expression.
This study also provided evidence that LXA4 phosphorylates Ser40 and triggers its nuclear translocation to activate Nrf2.
Moreover, when Nrf2-knockout (Nrf2-/-) mice and cells were used to further assess the effect of the Nrf2/HO-1 pathway, we found that Nrf2 expression knockdown partially eliminated the effect of LXA4 on the reductions in inflammatory factor levels while abrogating the inhibitory effect of LXA4 on the ROS generation stimulated by AP-ALI.
Overall, LXA4 attenuated the resolution of AP-induced inflammation and ROS generation to mitigate ALI, perhaps by modulating the Nrf2/HO-1 pathway.
These findings have laid a foundation for the treatment of AP-ALI.
American Psychological Association (APA)
Ye, Wen& Zheng, Chenlei& Yu, Dinglai& Zhang, Fan& Pan, Reguang& Ni, Xiao-feng…[et al.]. 2019. Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1202552
Modern Language Association (MLA)
Ye, Wen…[et al.]. Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1202552
American Medical Association (AMA)
Ye, Wen& Zheng, Chenlei& Yu, Dinglai& Zhang, Fan& Pan, Reguang& Ni, Xiao-feng…[et al.]. Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1202552
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202552