Acute Lung Injury Review

Tsushima, Kenji; King, Landon S.; Aggarwal, Neil R.; Gorordo, A De Basagoiti; D’Alessio, Franco R.; Kubo, Keishi

doi:10.2169/internalmedicine.48.1741

Cited by 274 publications

(235 citation statements)

References 40 publications

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“…This proinflammatory response will ultimately induce pulmonary circulation capillary leakage which will lead to non-cardiogenic pulmonary edema, hypoxemia, type II pneumocyte hyperplasia, and neutrophil infiltration. This stage of the disease is generally followed by increased fibroproliferation and hyaline membrane formation; depending on the patient, these gross pathological changes may progress or resolve [13]. Unfortunately, risk factors to identify patients at high risk for ARDS development are still matter of research [14].…”

mentioning

confidence: 99%

Severe viral pneumonia in adults: what is important for the ICU physician?

Gattarello

Rello

2017

Hospital Practice

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mentioning

confidence: 99%

Severe viral pneumonia in adults: what is important for the ICU physician?

Gattarello

Rello

2017

Hospital Practice

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“…Disruption of this vascular barrier induced by inflammatory agonists, such as IL-1b, TNF-a, and LPS, and by excessive mechanical stress, such as produced by shear stress or mechanical ventilation, leads to potentially lethal physiological dysfunction, such as hypoxemia and severe lung edema, which are hallmarks of acute inflammatory lung injury (ALI) (1)(2)(3). We previously demonstrated that MYLK, the gene encoding the critical cytoskeletal effector myosin light chain kinase (MLCK), is a compelling candidate gene in inflammatory lung injuries with critical modulation of vascular EC barrier integrity such as ALI and asthma (4)(5)(6).…”

mentioning

confidence: 99%

MicroRNA Regulation of Nonmuscle Myosin Light Chain Kinase Expression in Human Lung Endothelium

Adyshev

Moldobaeva

Mapes

et al. 2013

Am J Respir Cell Mol Biol

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Increased lung vascular permeability, the consequence of endothelial cell (EC) barrier dysfunction, is a cardinal feature of inflammatory conditions such as acute lung injury and sepsis and leads to lethal physiological dysfunction characterized by alveolar flooding, hypoxemia, and pulmonary edema. We previously demonstrated that the nonmuscle myosin light chain kinase isoform (nmMLCK) plays a key role in agonist-induced pulmonary EC barrier regulation. The present study evaluated posttranscriptional regulation of MYLK expression, the gene encoding nmMLCK, via 39 untranslated region (UTR) binding by microRNAs (miRNAs) with in silico analysis identifying hsa-miR-374a, hsa-miR-374b, hsa-miR-520c-3p, and hsa-miR-1290 as miRNA candidates. We identified increased MYLK gene transcription induced by TNF-a (24 h; 4.7 6 0.45 fold increase [FI]), LPS (4 h; 2.85 6 0.15 [FI]), and 18% cyclic stretch (24 h; 4.6 6 0.24 FI) that was attenuated by transfection of human lung ECs with mimics of hsa-miR-374a, hsa-miR-374b, hsa-miR-520c-3p, or hsa-miR-1290 (20-80% reductions by each miRNA). TNF-a, LPS, and 18% cyclic stretch each increased the activity of a MYLK 39UTR luciferase reporter (2.5-7.0 FI) with induction reduced by mimics of each miRNA (30-60% reduction). MiRNA inhibitors (antagomirs) for each MYLK miRNA significantly increased 39UTR luciferase activity (1.2-2.3 FI) and rescued the decreased MLCK-39UTR reporter activity produced by miRNA mimics (70-110% increases for each miRNA; P , 0.05). These data demonstrate that increased human lung EC expression of MYLK by bioactive agonists (excessive mechanical stress, LPS, TNF-a) is regulated in part by specific miRNAs (hsa-miR-374a, hsamiR-374b, hsa-miR-520c-3p, and hsa-miR-1290), representing a novel therapeutic strategy for reducing inflammatory lung injury.Keywords: miRNA; MLCK; acute lung injury; ventilator-induced lung injury; endothelial cellsThe pulmonary vascular endothelium serves as a semiselective barrier between circulating blood and surrounding tissues, with endothelial cell (EC) integrity being critical to tissue and organ function. Disruption of this vascular barrier induced by inflammatory agonists, such as IL-1b, TNF-a, and LPS, and by excessive mechanical stress, such as produced by shear stress or mechanical ventilation, leads to potentially lethal physiological dysfunction, such as hypoxemia and severe lung edema, which are hallmarks of acute inflammatory lung injury (ALI) (1-3). We previously demonstrated that MYLK, the gene encoding the critical cytoskeletal effector myosin light chain kinase (MLCK), is a compelling candidate gene in inflammatory lung injuries with critical modulation of vascular EC barrier integrity such as ALI and asthma (4-6). We cloned the full-length human MYLK gene encoding a novel nonmuscle MLCK isoform (nmMLCK) (210 kD) (7) and several nmMLCK splice variants that are also highly expressed in endothelium (8) and convincingly demonstrated nmMLCK as a multifunctional enzyme driving cytoskeletal participation in vascular barrier disrup...

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“…At present, ALI and acute respiratory distress syndrome are two types of respiratory diseases with high fatality rates (Maybauer et al, 2006;Tsushima et al, 2009). Sepsis can lead to the development of ALI (Xue et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The CLP method was used to create the ALI-sepsis rat model (Tsushima et al, 2009). The rats were anesthetized using 6% chloral hydrate (400 mg/kg).…”

Section: Modeling and Treatmentmentioning

confidence: 99%

Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression

Meng

et al. 2016

Genet. Mol. Res.

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ABSTRACT. This study aimed to explore the protective effect of quercetin on acute lung injury (ALI) in rats with sepsis and the related mechanism. Rats were administered different doses of quercetin intraperitoneally, and blood samples and lung tissue were collected at 24 h after treatment. Arterial blood gases, lung water content, protein content, and cell counts in bronchoalveolar lavage fluid (BALF) were measured. Morphological changes in lung tissue pathology were observed under a light microscope. Serum intercellular adhesion molecule (ICAM)-1 and macrophage inflammatory protein 2 (MIP-2) levels were detected and ICAM-1 and MIP-2 mRNA expression in lung tissue was determined. Compared with that in the control model group, arterial blood gases, lung water content, protein content, and cell counts in BALF improved in the high-and low-dose quercetin groups (P < 0.05), with maximal improvement observed for the highdose quercetin (P < 0.05). Lesions on the lungs improved in the high- and low-dose quercetin groups than those in the control model group, and the high-dose quercetin group showed better improvement than the low-dose group (P < 0.05). Compared with that in the sham-operated group, both serum and lung tissue ICAM-1 and MIP-2 expression increased significantly in the model group (P < 0.05). The quercetin groups presented lower ICAM-1 and MIP-2 expression than the control model group, with the lowest expression observed in the high-dose group (P < 0.05). Quercetin may protect against ALI in rats with sepsis by inhibiting ICAM-1 and MIP-2 expression.

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Acute Lung Injury Review

Abstract: The first report of acute respiratory distress syndrome (ARDS)

Cited by 274 publications

References 40 publications

Severe viral pneumonia in adults: what is important for the ICU physician?

Severe viral pneumonia in adults: what is important for the ICU physician?

MicroRNA Regulation of Nonmuscle Myosin Light Chain Kinase Expression in Human Lung Endothelium

Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression

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