scholarly journals MiR-574-5p alleviates sepsis-induced acute lung injury by regulating TRAF6/NF-κB pathway

2020 ◽  
Vol 19 (4) ◽  
pp. 676-682
Author(s):  
Changfu Xu ◽  
Lei Chong ◽  
Gang Yu ◽  
Hailin Zhang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cell ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Cytokine Expression ◽  
Inflammatory Cell Infiltration ◽  
Luciferase Assay ◽  
Cell Infiltration ◽  
Mice Model

Purpose: To investigate the protective effect of miR-574-5p pretreatment against acute lung injury (ALI) induced by sepsis.Methods: A male C57BL/6 mouse model of sepsis-induced ALI was established by cecal ligation and puncture (CLP) and treated with miR-574-5p agomir (intravenous injection, 80 mg/kg per day, 3 days). After that, blood and lung samples were obtained for histopathological observation. Myeloperoxidase (MPO) activity, inflammatory cell infiltration, and cytokine expression were analyzed. The target gene of miR-574-5p was predicted using TargetScan prediction, and verified by luciferase assay and western blot.Results: In sepsis-induced ALI mice model, downregulation of miR-574-5p was observed. Pretreatment of miR-574-5p significantly alleviated ALI by suppressing histological damage, and reducing MPO activity and inflammatory cell infiltration, as well as decreasing cytokine expression. The  underlying mechanism was that miR-574-5p targeted TNF receptor associated factor 6 (TRAF6) and suppressed the downstream NF-κB pathway. Moreover, TRAF6 overexpression reversed the effects of miR-574-5p on ALI.Conclusion: MiR-574-5p pretreatment suppresses inflammatory responses, thus reducing lung injury induced by sepsis in mice, partly via the regulation of TRAF6 and NF-κB pathway. Therefore, this approach can potentially be used for the clinical management of ALI in humans Keywords: Sepsis, Acute lung injury, MiR-574-5p, TRAF6, NF-κB pathway

scholarly journals Protein S is Protective in Acute Lung Injury by Inhibiting Cell Apoptosis

2019 ◽  
Vol 20 (5) ◽  
pp. 1082 ◽  
Author(s):  
Prince Baffour Tonto ◽  
Taro Yasuma ◽  
Tetsu Kobayashi ◽  
Corina D’Alessandro-Gabazza ◽  
Masaaki Toda ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Transgenic Mice ◽  
Lung Tissue ◽  
Cell Apoptosis ◽  
Inflammatory Cell ◽  
Protein S ◽  
Inflammatory Cell Infiltration ◽  
Human Protein ◽  
Wild Type

Acute lung injury is a fatal disease characterized by inflammatory cell infiltration, alveolar-capillary barrier disruption, protein-rich edema, and impairment of gas exchange. Protein S is a vitamin K-dependent glycoprotein that exerts anticoagulant, immunomodulatory, anti-inflammatory, anti-apoptotic, and neuroprotective effects. The aim of this study was to evaluate whether human protein S inhibits cell apoptosis in acute lung injury. Acute lung injury in human protein S transgenic and wild-type mice was induced by intratracheal instillation of lipopolysaccharide. The effect of human protein S on apoptosis of lung tissue cells was evaluated by Western blotting. Inflammatory cell infiltration, alveolar wall thickening, myeloperoxidase activity, and the expression of inflammatory cytokines were reduced in human protein S transgenic mice compared to the wild-type mice after lipopolysaccharide instillation. Apoptotic cells and caspase-3 activity were reduced while phosphorylation of extracellular signal-regulated kinase was enhanced in the lung tissue from human protein S transgenic mice compared to wild-type mice after lipopolysaccharide instillation. The results of this study suggest that human protein S is protective in lipopolysaccharide-induced acute lung injury by inhibiting apoptosis of lung cells.

scholarly journals GPA Peptide Attenuates Sepsis-Induced Acute Lung Injury in Mice via Inhibiting Oxidative Stress and Pyroptosis of Alveolar Macrophage

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yukun Liu ◽  
Yongsheng Zhang ◽  
Quanrui Feng ◽  
Qinxin Liu ◽  
Jie Xie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophage ◽  
Inflammatory Cell ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Cecal Ligation ◽  
Regulatory Function ◽  
Protective Effects

Acute lung injury (ALI) has been known to be a devastating form of respiratory infection and an important contributor to mortality in intensive care, due to its lacking of effective treatment. Inflammation, oxidative stress, and pyroptosis are associated with multiple kinds of inflammatory diseases such as ALI. It is commonly accepted that Gly-Pro-Ala (GPA) peptide regulates oxidative stress and pyroptosis in different kinds of inflammatory diseases. Our study is aimed at exploring the regulatory function and protective effects of GPA peptides on ALI. In the current study, the cecal ligation and puncture (CLP) technique was used to evoke sepsis in mice, and GPA peptide was administered intraperitoneally with different concentrations (50, 100, and 150 mg/kg) after CLP. Histopathological changes and the ratio of wet-to-dry in lung were recorded and analyzed. We also investigated the level of oxidative stress, inflammation, and pyroptosis. Results showed that GPA peptide significantly ameliorated CLP-stimulated lung tissue injury, impeded proinflammatory cytokine release, and reduced inflammatory cell infiltration. Additionally, GPA peptide suppressed oxidative stress and caspase-1-dependent pyroptosis in alveolar macrophages. Furthermore, our study showed that the GPA peptide prevents alveolar macrophage from undergoing pyroptosis by attenuating ROS. In conclusion, results demonstrated that GPA peptide has protective effects in CLP-stimulated ALI by inhibiting oxidative stress as well as pyroptosis of alveolar macrophage.

scholarly journals Attenuation of lipopolysaccharide-induced lung inflammation by ascorbic acid in rats: Histopathological and ultrastructural study

2019 ◽  
Vol 7 ◽  
pp. 205031211982826 ◽  
Author(s):  
Hazem Abdelhamid Mohamed ◽  
Yasser M Elbastawisy ◽  
Wael M Elsaed
Keyword(s):  
Ascorbic Acid ◽  
Basement Membrane ◽  
Lung Injury ◽  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Group Iii ◽  
Ultrastructural Studies ◽  
Group I ◽  
Group Ii

Introduction: Lipopolysaccharide is a bacterial endotoxin that induces acute lung injury in experimental animals, which is similar to acute respiratory distress syndrome in humans. The induced tissue trauma ends in fibrosis. Understanding the pathogenesis is important in the prevention and treatment of the complications. This study was assigned to investigate the long-term lipopolysaccharide-induced lung injury and the postulated protective effect of ascorbic acid on these changes. Materials and methods: Twenty-four adult male albino rats were divided into three groups. Group I was the controls, group II received lipopolysaccharide and group III received lipopolysaccharide and ascorbic acid. After 30 days of starting treatment, lung tissue samples were obtained. Results: Group II lung tissues showed marked thickening of the alveolar septa with collapsed alveolar sacs, detached bronchial epithelium, inflammatory cell infiltration and excessive deposition of collagen. Group III showed mild thickening of the alveolar walls, scanty inflammatory cell infiltration, mild parabronchial fibrosis and less marked collagen deposition. α-Smooth muscle actin staining of group II showed marked expression of the actin-positive cells. Less potential expression of the dye was found in group III. Ultrastructural examination of group II showed evident structural changes in pneumocytes with capillary basement membrane irregularity and interruption compared to uniform basement membrane in group III with less prominent intracellular changes in pneumocytes. Conclusion: Ascorbic acid attenuated the inflammatory response and fibrosis in the lungs of rats treated with lipopolysaccharide as evidenced by the histological, immunohistochemical and ultrastructural studies.

scholarly journals PDX regulates inflammatory cell infiltration via resident macrophage in LPS‐induced lung injury

2020 ◽  
Vol 24 (18) ◽  
pp. 10604-10614
Author(s):  
Yang Ye ◽  
Hua‐Wei Zhang ◽  
Hong‐Xia Mei ◽  
Hao‐Ran Xu ◽  
Shu‐Yang Xiang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Resident Macrophage

scholarly journals Ghrelin attenuates sepsis-induced acute lung injury by inhibiting the NF-κB, iNOS, and Akt signaling in alveolar macrophages

2019 ◽  
Vol 317 (3) ◽  
pp. L381-L391 ◽  
Author(s):  
Haichong Zheng ◽  
Wenjie Liang ◽  
Wanmei He ◽  
Chunrong Huang ◽  
Qingui Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Cecal Ligation ◽  
Protective Role ◽  
Akt Signaling ◽  
Cytokines And Chemokines

Ghrelin has proven to be protective against sepsis-induced acute lung injury (ALI) via anti-inflammatory effects. However, its mechanisms remain poorly understood. Alveolar macrophages (AMs) play a key role in mediating inflammatory responses during sepsis-induced ALI by secretion of cytokines and chemokines. This study was undertaken to investigate whether ghrelin suppresses inflammatory effects of AMs and therefore may help to attenuate sepsis-induced ALI. A sepsis model in rats was achieved using cecal ligation and puncture. Ghrelin treatment markedly improved histopathological changes in the lungs and reduced pulmonary inflammation in septic rats. NF-κB translocation and p-Akt and inducible nitric oxide synthase (iNOS) activities in AMs from septic rats were suppressed by ghrelin. In vitro data indicated that ghrelin decreased the levels of LPS-induced IL-1β, TNF-α, and IL-6, NF-κB translocation, and iNOS and Akt activities of AMs. Furthermore, the NF-κB/iNOS pathway or Akt signaling was positively correlated with LPS-induced inflammatory production of AMs in vitro. In conclusion, ghrelin exerts a protective role against sepsis-induced ALI probably by reducing the production of inflammatory cytokines from AMs via inhibition of the NF-κB/iNOS pathway or Akt signaling.

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