MCTR3 reduces LPS-induced acute lung injury in mice via the ALX/PINK1 signaling pathway
| Autor: | Zhongqiu Lu, Yingying Sun, Wenchao Cai, Guangju Zhao, Liang Lv, Rongxiao Xu, Yayong Guo, Rong Zhuang, Jingjing Ni, Xiyu Yang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Programmed cell death medicine.medical_treatment Acute Lung Injury Immunology Anti-Inflammatory Agents Apoptosis Inflammation Lung injury Pharmacology medicine.disease_cause Cell Line Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine medicine Animals Immunology and Allergy Adaptor Proteins Signal Transducing business.industry Epithelial Cells respiratory system Mitochondria respiratory tract diseases Mice Inbred C57BL Endothelial stem cell Disease Models Animal Oxidative Stress 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Cytokines Inflammation Mediators medicine.symptom business Protein Kinases Oxidative stress Signal Transduction |
| Zdroj: | International Immunopharmacology. 90:107142 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2020.107142 |
| Popis: | Acute lung injury (ALI), a common respiratory distress syndrome in the intensive care unit (ICU), is mainly caused by severe infection and shock. Epithelial and capillary endothelial cell injury, interstitial edema and inflammatory cell infiltration are the main pathological changes observed in ALI animal models. Maresin conjugates in tissue regeneration (MCTR) are a new family of anti-inflammatory proteins. MCTR3 is a key enhancer of the host response, that promotes tissue regeneration and reduces infection; however, its role and mechanism in ALI are still unclear. The purpose of our research was to assess the protective effects of MCTR3 against ALI and its underlying mechanism. The work in this study was conducted in a murine model and the pulmonary epithelial cell line MLE-12. In vivo, MCTR3 (2 ng/g) was given 2 h after lipopolysaccharide (LPS) injection. We found that the treatment of mice with LPS-induced ALI with MCTR3 significantly reduced the cell number and protein levels in the bronchoalveolar lavage fluid (BALF); decreased the production of inflammatory cytokines; alleviated oxidative stress and cell apoptosis, consequently decreased lung injury; and restored pulmonary function. These protective effects of MCTR3 were dependent on down-regulation of the PTEN-induced putative kinase 1 (PINK1) pathway. Additionally, in MLE-12 cells stimulated with LPS, MCTR3 inhibited cell death, inflammatory cytokine levels and oxidative stress via the ALX/PINK1 signaling pathway. Thus, we conclude that MCTR3 protected against LPS-induced ALI partly through inactivation of the ALX/PINK1 mediated mitophagy pathway. |
| Databáze: | OpenAIRE |
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