scholarly journals miR-221-5p-Mediated Downregulation of JNK2 Aggravates Acute Lung Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Yang ◽  
Hanh Chi Do-Umehara ◽  
Qiao Zhang ◽  
Huashan Wang ◽  
Changchun Hou ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mitochondrial Dysfunction ◽  
Lung Inflammation ◽  
Endotoxic Shock ◽  
Small Rna Sequencing ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Sequence Matching ◽  
Cell Counts

Sepsis and acute lung injury (ALI) are linked to mitochondrial dysfunction; however, the underlying mechanism remains elusive. We previously reported that c-Jun N-terminal protein kinase 2 (JNK2) promotes stress-induced mitophagy by targeting small mitochondrial alternative reading frame (smARF) for ubiquitin-mediated proteasomal degradation, thereby preventing mitochondrial dysfunction and restraining inflammasome activation. Here we report that loss of JNK2 exacerbates lung inflammation and injury during sepsis and ALI in mice. JNK2 is downregulated in mice with endotoxic shock or ALI, concomitantly correlated inversely with disease severity. Small RNA sequencing revealed that miR-221-5p, which contains seed sequence matching to JNK2 mRNA 3’ untranslated region (3’UTR), is upregulated in response to lipopolysaccharide, with dynamically inverse correlation with JNK2 mRNA levels. miR-221-5p targets the 3’UTR of JNK2 mRNA leading to its downregulation. Accordingly, miR-221-5p exacerbates lung inflammation and injury during sepsis in mice by targeting JNK2. Importantly, in patients with pneumonia in medical intensive care unit, JNK2 mRNA levels in alveolar macrophages flow sorted from non-bronchoscopic broncholaveolar lavage (BAL) fluid were inversely correlated strongly and significantly with the percentage of neutrophils, neutrophil and white blood cell counts in BAL fluid. Our data suggest that miR-221-5p targets JNK2 and thereby aggravates lung inflammation and injury during sepsis.

Inflammasome Activation in Acute Lung Injury

2020 ◽  
Author(s):  
Mark John McVey ◽  
Benjamin Ethan Steinberg ◽  
Neil M Goldenberg
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Translational Research ◽  
Lung Inflammation ◽  
Distress Syndrome ◽  
Protein Complexes ◽  
Lung Parenchyma ◽  
Inflammasome Activation ◽  
Future Directions ◽  
Inflammatory Signals

Inflammasomes are multi-protein complexes tasked with sensing endogenous or exogenous inflammatory signals, and integrating this signal into a downstream response. Inflammasome activation has been implicated in a variety of pulmonary diseases, including pulmonary hypertension, bacterial pneumonia, COPD and asthma. Of increasing interest is the contribution of inflammasome activation in the context of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Inflammasome activation in both the lung parenchyma and resident immune cells generates intereukin-1β (IL-1β) and IL-18, both of which drive the cascade of lung inflammation forward. Blockade of these responses has been shown to be beneficial in animal models, and is a focus of translational research in the field. In this review, we will discuss the assembly and regulation of inflammasomes during lung inflammation, highlighting therapeutically-viable effector steps. We will examine the importance of IL-1β and IL-18, two key products of inflammasome activation, in ALI, as well as the contribution of the pulmonary endothelial cell to this process. Finally, we will explore translational research moving toward anti-inflammasome therapies for ALI/ARDS, and speculate toward future directions for the field.

scholarly journals Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration–induced Lung Injury

2012 ◽  
Vol 117 (6) ◽  
pp. 1322-1334 ◽  
Author(s):  
Aline M. Ambrosio ◽  
Rubin Luo ◽  
Denise T. Fantoni ◽  
Claudia Gutierres ◽  
Qin Lu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Recruitment Maneuver ◽  
Alveolar Wall ◽  
Arterial Oxygenation ◽  
Positive End Expiratory Pressure ◽  
Acid Aspiration ◽  
Recruitment Maneuvers ◽  
Alveolar Area

Background In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

scholarly journals miR-34b-5p inhibition attenuates lung inflammation and apoptosis in an LPS-induced acute lung injury mouse model by targeting progranulin

2018 ◽  
Vol 233 (9) ◽  
pp. 6615-6631 ◽  
Author(s):  
Wang Xie ◽  
Qingchun Lu ◽  
Kailing Wang ◽  
Jingjing Lu ◽  
Xia Gu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Lung Inflammation

Vanillin protects lipopolysaccharide-induced acute lung injury by inhibiting ERK1/2, p38 and NF-κB pathway

2019 ◽  
Vol 11 (16) ◽  
pp. 2081-2094 ◽  
Author(s):  
Tingting Guo ◽  
Zhenzhong Su ◽  
Qi Wang ◽  
Wei Hou ◽  
Junyao Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blot ◽  
Lung Inflammation ◽  
Macrophage Activation ◽  
Myeloperoxidase Activity ◽  
Histopathological Changes ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Aim: Thus far, the anti-inflammatory effect of vanillin in acute lung injury (ALI) has not been studied. This study aimed to investigate the effect of vanillin in lipopolysaccharide (LPS)-induced ALI. Results & methodology: Our study detected the anti-inflammatory effects of vanillin by ELISA and western blot, respectively. Pretreatment of mice with vanillin significantly attenuated LPS-stimulated lung histopathological changes, myeloperoxidase activity and expression levels of proinflammatory cytokines by inhibiting the phosphorylation activities of ERK1/2, p38, AKT and NF-κB p65. In addition, vanillin inhibited LPS-induced TNF-α and IL-6 expression in RAW264.7 cells via ERK1/2, p38 and NF-κB signaling. Conclusion: Vanillin can inhibit macrophage activation and lung inflammation, which suggests new insights for clinical treatment of ALI.

scholarly journals The Crucial Role of PPARγ-Egr-1-Pro-Inflammatory Mediators Axis in IgG Immune Complex-Induced Acute Lung Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunguang Yan ◽  
Jing Chen ◽  
Yue Ding ◽  
Zetian Zhou ◽  
Bingyu Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Complex ◽  
Inflammatory Mediators ◽  
Lung Inflammation ◽  
Acute Lung Inflammation ◽  
Pparγ Agonist

BackgroundThe ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays crucial roles in diverse biological processes including cellular metabolism, differentiation, development, and immune response. However, during IgG immune complex (IgG-IC)-induced acute lung inflammation, its expression and function in the pulmonary tissue remains unknown.ObjectivesThe study is designed to determine the effect of PPARγ on IgG-IC-triggered acute lung inflammation, and the underlying mechanisms, which might provide theoretical basis for therapy of acute lung inflammation.SettingDepartment of Pathogenic Biology and Immunology, Medical School of Southeast UniversitySubjectsMice with down-regulated/up-regulated PPARγ activity or down-regulation of Early growth response protein 1 (Egr-1) expression, and the corresponding controls.InterventionsAcute lung inflammation is induced in the mice by airway deposition of IgG-IC. Activation of PPARγ is achieved by using its agonist Rosiglitazone or adenoviral vectors that could mediate overexpression of PPARγ. PPARγ activity is suppressed by application of its antagonist GW9662 or shRNA. Egr-1 expression is down-regulated by using the gene specific shRNA.Measures and Main ResultsWe find that during IgG-IC-induced acute lung inflammation, PPARγ expression at both RNA and protein levels is repressed, which is consistent with the results obtained from macrophages treated with IgG-IC. Furthermore, both in vivo and in vitro data show that PPARγ activation reduces IgG-IC-mediated pro-inflammatory mediators’ production, thereby alleviating lung injury. In terms of mechanism, we observe that the generation of Egr-1 elicited by IgG-IC is inhibited by PPARγ. As an important transcription factor, Egr-1 transcription is substantially increased by IgG-IC in both in vivo and in vitro studies, leading to augmented protein expression, thus amplifying IgG-IC-triggered expressions of inflammatory factors via association with their promoters.ConclusionDuring IgG-IC-stimulated acute lung inflammation, PPARγ activation can relieve the inflammatory response by suppressing the expression of its downstream target Egr-1 that directly binds to the promoter regions of several inflammation-associated genes. Therefore, regulation of PPARγ-Egr-1-pro-inflammatory mediators axis by PPARγ agonist Rosiglitazone may represent a novel strategy for blockade of acute lung injury.

scholarly journals The effects of Gamijinhae-tang on elastase/lipopolysaccharide-induced lung inflammation in an animal model of acute lung injury

2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Sung-Hwa Sohn ◽  
HaRyeon Jang ◽  
Youngeun Kim ◽  
Young Pyo Jang ◽  
Seung-Hun Cho ◽  
...  
Keyword(s):  
Animal Model ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation

scholarly journals Photobiomodulation prevents DNA fragmentation of alveolar epithelial cells and alters the mRNA levels of caspase 3 and Bcl-2 genes in acute lung injury

2018 ◽  
Vol 17 (7) ◽  
pp. 975-983 ◽  
Author(s):  
Luiz Philippe da Silva Sergio ◽  
Andrezza Maria Côrtes Thomé ◽  
Larissa Alexsandra da Silva Neto Trajano ◽  
Andre Luiz Mencalha ◽  
Adenilson de Souza da Fonseca ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Alveolar Epithelial Cells ◽  
Mrna Levels ◽  
Alveolar Epithelial ◽  
Life Threatening ◽  
Pulmonary Permeability

Acute lung injury (ALI) is defined as hyperinflammation that could occur from sepsis and lead to pulmonary permeability and edema, making them life-threatening diseases.

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