Beneficial Effect of Etanercept on Hyperoxic Lung Injury Model in Neonatal Rats

Öncel, Mehmet Yekta; Yurttutan, Sadık; Dizdar, Evrim Alyamaç; Gökçe, İsmail Kürşat; Gönül, İpek Işık; Topal, Turgut; Canpolat, Fuat Emre; Dilmen, Uğur

doi:10.3109/08941939.2015.1034898

Cited by 15 publications

(10 citation statements)

References 20 publications

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“…As expected, tracheal aspirates of infants exposed to hyperoxia had elevated inflammatory mediators primarily secreted by macrophages, notably IL-1b and tumor necrosis factor-a (14,15). In infants with sepsis-induced inflammation, inhibitors against the two cytokines showed little improvement in survival rates; in mouse models treated with inhibitors against these cytokines, only some BPD features improved (16)(17)(18)(19)(20). This suggests that alternative, more broadly functioning or upstream targets are needed to prevent BPD.…”

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confidence: 80%

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Lee

Lal

Persad

et al. 2016

Am J Respir Cell Mol Biol

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Myeloid cells are key factors in the progression of bronchopulmonary dysplasia (BPD) pathogenesis. Endothelial monocyte-activating polypeptide II (EMAP II) mediates myeloid cell trafficking. The origin and physiological mechanism by which EMAP II affects pathogenesis in BPD is unknown. The objective was to determine the functional consequences of elevated EMAP II levels in the pathogenesis of murine BPD and to investigate EMAP II neutralization as a therapeutic strategy. Three neonatal mouse models were used: (1) BPD (hyperoxia), (2) EMAP II delivery, and (3) BPD with neutralizing EMAP II antibody treatments. Chemokinic function of EMAP II and its neutralization were assessed by migration in vitro and in vivo. We determined the location of EMAP II by immunohistochemistry, pulmonary proinflammatory and chemotactic gene expression by quantitative polymerase chain reaction and immunoblotting, lung outcome by pulmonary function testing and histological analysis, and right ventricular hypertrophy by Fulton's Index. In BPD, EMAP II initially is a bronchial clubcell-specific protein-derived factor that later is expressed in galectin-3 1 macrophages as BPD progresses. Continuous elevated expression corroborates with baboon and human BPD. Prolonged elevation of EMAP II levels recruits galectin-3 1 macrophages, which is followed by an inflammatory state that resembles a severe BPD phenotype characterized by decreased pulmonary compliance, arrested alveolar development, and signs of pulmonary hypertension. In vivo pharmacological EMAP II inhibition suppressed proinflammatory genes Tnfa, Il6, and Il1b and chemotactic genes Ccl2 and Ccl9 and reversed the severe BPD phenotype. EMAP II is sufficient to induce macrophage recruitment, worsens BPD progression, and represents a targetable mechanism of BPD development.

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confidence: 80%

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Lee

Lal

Persad

et al. 2016

Am J Respir Cell Mol Biol

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“…In BPD models of hyperoxia-exposed neonatal rats, the levels of a variety of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, increased [5–7]. Previous studies have demonstrated that some agents, such as etanercept [8], colchicine [9], and caffeine [10], had favorable effects on alveolarization and/or lung function by alleviating inflammation response in hyperoxia-exposed neonatal rats with BPD.…”

Section: Introductionmentioning

confidence: 99%

Human β-Defensin-2 Improves Hyperoxia-Induced Lung Structural and Functional Injury in Neonatal Rats

Sun

Chen²,

et al. 2019

Med Sci Monit

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Background Bronchopulmonary dysplasia (BPD) is a major complication of extreme prematurity, characterized by alveolar simplification and pulmonary malfunction. Hyperoxia-induced lung injury in neonatal rats has been used as a model of BPD, as indicated by lung architectural change and alveolar simplification that resembles clinical feature of BPD. β-defensin-2 (BD2) plays an important role in lung diseases by inhibiting inflammation response. However, little is known about its role in BPD. The aim of this study was to determine the effect of human BD2 (hBD2) gene on hyperoxia-induced animal model of BPD. Material/Methods The neonatal rats were exposed to 90% oxygen (O 2 ) continuously for 14 days to mimic the BPD-like lung injury. These rats were then randomly assigned to the following four groups: in room air (air), in 90% O 2 , in 90% O 2 with null adenovirus vector infection (O 2 +Ad), and in 90% O 2 with gene therapy through adenovirus transfected hBD2 (O 2 +Ad-hBD2). Morphology of lungs, pulmonary function and expression of inflammatory cytokines on P7, P10, P14, and P21 were documented and compared across the 4 groups. Results The overexpression of hBD2 mediated by the adenovirus vector was successfully constructed. hBD2 gene therapy increased hBD2 mRNA expression, increased radial alveolar count (RAC), lung volume and compliance, decreased mean linear intercept (MLI), tissue damping, and elastance. Furthermore, pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were inhibited and anti-inflammatory cytokines IL-10 was increased in the lungs of rats in O 2 +Ad-hBD2 group. Conclusions In hyperoxia-induced rat models of BPD, hBD2 promotes alveolarization and improves pulmonary function. The mechanism may contribute in alleviating inflammation response and inhibiting pro-inflammatory factors including IL-1β, IL-6, and TNF-α.

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“…Experiments in neonatal rats have shown that the inhibition of inflammatory factors is beneficial for treating alveolar and lung injury by reducing lung inflammation and oxidative stress. For example, the inhibition of TNF- α can decrease the levels of MDA, which is helpful for lung development and pulmonary vascularization ( 37 ). IL-1 β , IL-6, and MCP-1 are also identified as the biomarkers in monitoring ALI ( 35 , 36 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

Intratracheal Transplantation of Amnion-Derived Mesenchymal Stem Cells Ameliorates Hyperoxia-Induced Neonatal Hyperoxic Lung Injury via Aminoacyl-Peptide Hydrolase

Gong

Dong

et al. 2020

IJSC

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Background and Objectives: Bronchopulmonary dysplasia (BPD) has major effects in premature infants. Although previous literature has indicated that mesenchymal stem cells (MSCs) can alleviate lung pathology in BPD newborns and improve the survival rate, few research have been done investigating significantly differentially expressed genes in the lungs before and after MSCs therapy. The aim of this study is to identify differentially expressed genes in lung tissues before and after hAD-MSC treatment. Methods and Results: Human amnion-derived MSCs (hAD-MSCs) were cultured and met the MSCs criteria for cell phenotype and multidirectional differentiation. Then we confirmed the size of hAD-MSCs-EXOs and their expressed markers. An intratracheal drip of living cells showed the strongest effect on NHLI compared to cellular secretions or exosomes, both in terms of ameliorating pulmonary edema and reducing inflammatory cell infiltration. Through gene chip hybridization, PCR, and western blotting, acylaminoacyl-peptide hydrolase (APEH) expression was found to be significantly decreased under hyperoxia, and significantly increased after hAD-MSC treatment. Conclusions: The intratracheal transplantation of hAD-MSCs ameliorated NHLI in neonatal rats through APEH.

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Beneficial Effect of Etanercept on Hyperoxic Lung Injury Model in Neonatal Rats

Abstract: Etanercept has favorable effects on alveolarization as well as inflammation and oxidative stress markers in a neonatal rat model of BPD.

Cited by 15 publications

References 20 publications

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Human β-Defensin-2 Improves Hyperoxia-Induced Lung Structural and Functional Injury in Neonatal Rats

Intratracheal Transplantation of Amnion-Derived Mesenchymal Stem Cells Ameliorates Hyperoxia-Induced Neonatal Hyperoxic Lung Injury via Aminoacyl-Peptide Hydrolase

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