Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System
| Autor: | Xin-Qi Wang, Min Zhou, Ji-Wei Hao, Guang-Lei Li, Ning Dong, Xiao-Jing Ji, Yong-ming Yao, Qing-Hong Zhang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine endocrine system Burn injury medicine.medical_specialty Sympathetic nervous system Sympathetic Nervous System Article Subject T-Lymphocytes T cell Immunology Inflammation Propranolol complex mixtures Glucagon-Like Peptide-1 Receptor Mice 03 medical and health sciences fluids and secretions 0302 clinical medicine Glucagon-Like Peptide 1 In vivo Internal medicine lcsh:Pathology medicine Animals Mice Inbred BALB C business.industry digestive oral and skin physiology Antagonist NFAT Cell Biology 030104 developmental biology medicine.anatomical_structure Endocrinology Exenatide medicine.symptom Burns business hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery lcsh:RB1-214 Research Article medicine.drug |
| Zdroj: | Mediators of Inflammation Mediators of Inflammation, Vol 2019 (2019) |
| ISSN: | 1466-1861 0962-9351 |
| DOI: | 10.1155/2019/2750528 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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