Xiaolong Zhang1, Rong Zhuang1, Haiya Wu1, Jie Chen1, Fangyan Wang2, Guoping Li3, Chengyun Wu4. 1. Department of Anesthesiology, Critical Care and Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Western Road, Wenzhou, Zhejiang Province 325027, PR China. 2. Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, PR China. 3. Department of Respiratory Medicine Tongde Hospital of Zhejiang Province, PR China. Electronic address: wzmclgp@163.com. 4. Department of Respiratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, PR China. Electronic address: wcy857516126@163.com.
Abstract
AIMS: Endotoxin induced acute lung injury (ALI) is a critical complication of some clinical illnesses. Endothelial cell dysfunction and excessive pro-inflammation cytokine release are pivotal to the injury of alveolar-capillary membrane which is the typical characteristic of endotoxic lung injury. As a potential marker of endothelial cells, endocan plays an important role in many endothelial-dependent pathophysiological diseases. We speculated that endocan have anti-inflammatory property in ALI. Here, we investigated the role of endocan in LPS-induced ALI. MATERIALS AND METHODS: Mice were randomly divided into 4 groups. LPS were used to construct ALI mice model by aerosolization for 20 min. Endocan was intraperitoneal injected at 30 min before LPS exposure. Levels of TNF-α, IFN-γ, IL-1β, IL-6 and MPO activities were detected by indicated ELISA. Cell apoptotic rate was determined by Annexin V/PI kit, ROS level and MPTP were detected by DCFH-DA and JC-1 kit, respectively. Seahorse XF96 was applied to evaluate the alteration of OCR and ECAR. Western blot and qRT-PCR were used to detect indicated molecules. KEY FINDINGS: Endocan effectively decreased TNF-α, IFN-γ, IL-1β, and IL-6 levels as well as relieved pulmonary epithelium cell apoptosis caused by LPS exposure. Endocan significantly reversed LPS induced UPRmt and promoted cell metabolism reprogramming which were crucial for the protective characteristic of endocan in ALI mice model. SIGNIFICANCE: The above findings suggested endocan could significantly suppress inflammatory response in ALI model through attenuating UPRmt associated apoptosis and switch cellular bioenergetics, indicating endocan could be considered as a promising compound against LPS induced ALI.
AIMS: Endotoxin induced acute lung injury (ALI) is a critical complication of some clinical illnesses. Endothelial cell dysfunction and excessive pro-inflammation cytokine release are pivotal to the injury of alveolar-capillary membrane which is the typical characteristic of endotoxic lung injury. As a potential marker of endothelial cells, endocan plays an important role in many endothelial-dependent pathophysiological diseases. We speculated that endocan have anti-inflammatory property in ALI. Here, we investigated the role of endocan in LPS-induced ALI. MATERIALS AND METHODS:Mice were randomly divided into 4 groups. LPS were used to construct ALI mice model by aerosolization for 20 min. Endocan was intraperitoneal injected at 30 min before LPS exposure. Levels of TNF-α, IFN-γ, IL-1β, IL-6 and MPO activities were detected by indicated ELISA. Cell apoptotic rate was determined by Annexin V/PI kit, ROS level and MPTP were detected by DCFH-DA and JC-1 kit, respectively. Seahorse XF96 was applied to evaluate the alteration of OCR and ECAR. Western blot and qRT-PCR were used to detect indicated molecules. KEY FINDINGS: Endocan effectively decreased TNF-α, IFN-γ, IL-1β, and IL-6 levels as well as relieved pulmonary epithelium cell apoptosis caused by LPS exposure. Endocan significantly reversed LPS induced UPRmt and promoted cell metabolism reprogramming which were crucial for the protective characteristic of endocan in ALI mice model. SIGNIFICANCE: The above findings suggested endocan could significantly suppress inflammatory response in ALI model through attenuating UPRmt associated apoptosis and switch cellular bioenergetics, indicating endocan could be considered as a promising compound against LPS induced ALI.
Authors: Nathalie De Freitas Caires; Alexandre Gaudet; Lucie Portier; Anne Tsicopoulos; Daniel Mathieu; Philippe Lassalle Journal: Crit Care Date: 2018-10-26 Impact factor: 9.097