Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System
Joint Authors
Yao, Yong-Ming
Ji, Xiao-Jing
Hao, Ji-Wei
Li, Guang-Lei
Dong, Ning
Wang, Xin-Qi
Zhou, Min
Zhang, Qing-Hong
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-01-17
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Background.
Although glucagon-like peptide 1- (GLP-1-) based therapy of hyperglycemia in burn injury has shown great potential in clinical trials, its safety is seldom evaluated.
We hypothesize that exendin-4, a GLP-1 analogue, might affect the immune response via the activation of the sympathetic nervous system in burn injury.
Methods.
Male Balb/c mice were subjected to sham or thermal injury of 15% total body surface area.
Exendin-4 on T cell function in vitro was examined in cultured splenocytes in the presence of β-adrenoceptor antagonist propranolol (1 nmol/L) or GLP-1R antagonist exendin (9-39) (1 μmol/L), whereas its in vivo effect was determined by i.p.
injection of exendin-4 (2.4 nmol/kg) in mice.
To further elucidate the sympathetic mechanism, propranolol (30 mg/kg) or vehicle was applied 30 min prior to injury.
Results.
Although the exacerbated burn-induced mortality by exendin-4 was worsened by propranolol pretreatment, the inhibition of T cell proliferation by exendin-4 in vitro could be restored by propranolol instead of exendin (9-39).
However, a Th2 switch by exendin-4 in vitro could only be reversed by exendin (9-39).
Likewise, the inhibition of splenic T cell function and NFAT activity by exendin-4 in vivo was restored by propranolol.
By contrast, the increased splenic NF-κB translocation by exendin-4 in vivo was potentiated by propranolol in sham mice but suppressed in burn mice.
Accordingly, propranolol abrogated the heightened inflammatory response in the lung and the accelerated organ injuries by exendin-4 in burn mice.
On the contrary, a Th2 switch and higher serum levels of inflammatory mediators by exendin-4 were potentiated by propranolol in burn mice.
Lastly, exendin-4 raised serum stress hormones which could be remarkably augmented by propranolol.
Conclusions.
Exendin-4 suppresses T cell function and promotes organ inflammation through the activation of the sympathetic nervous system, while elicits Th2 switch via GLP-1R in burn injury.
American Psychological Association (APA)
Ji, Xiao-Jing& Hao, Ji-Wei& Li, Guang-Lei& Dong, Ning& Wang, Xin-Qi& Zhou, Min…[et al.]. 2019. Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System. Mediators of Inflammation،Vol. 2019, no. 2019, pp.1-16.
https://search.emarefa.net/detail/BIM-1192730
Modern Language Association (MLA)
Ji, Xiao-Jing…[et al.]. Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System. Mediators of Inflammation No. 2019 (2019), pp.1-16.
https://search.emarefa.net/detail/BIM-1192730
American Medical Association (AMA)
Ji, Xiao-Jing& Hao, Ji-Wei& Li, Guang-Lei& Dong, Ning& Wang, Xin-Qi& Zhou, Min…[et al.]. Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-16.
https://search.emarefa.net/detail/BIM-1192730
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192730