A Peptide Inhibitor of NADPH Oxidase (NOX2) Activation Markedly Decreases Mouse Lung Injury and Mortality Following Administration of Lipopolysaccharide (LPS)

Fisher, Aron B.; Dodia, Chandra; Chatterjee, Shampa; Feinstein, Sheldon I.

doi:10.3390/ijms20102395

Cited by 28 publications

(39 citation statements)

References 52 publications

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“…Considerably increased levels of intracellular ROS and nitric oxide (NO) were also present in A549 cells after LPS treatment [12]. LPS induces ROS production possibly through the activation of NADPH oxidase 2 which is responsible for generating the highly reactive superoxide radical (O 2 − ) or hydrogen peroxide (H 2 O 2 ) as a primary product [45,46]. ROS further enhance the activation of various stress kinases and redox-sensitive transcription factors such as NF-κB [43,47].…”

Section: Discussionmentioning

confidence: 99%

Short-Term versus Long-Term Culture of A549 Cells for Evaluating the Effects of Lipopolysaccharide on Oxidative Stress, Surfactant Proteins and Cathelicidin LL-37

Nová

Škovierová

Strnádel

et al. 2020

IJMS

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Alveolar epithelial type II (ATII) cells and their proper function are essential for maintaining lung integrity and homeostasis. However, they can be damaged by lipopolysaccharide (LPS) during Gram-negative bacterial infection. Thus, this study evaluated and compared the effects of LPS on short and long-term cultures of A549 cells by determining the cell viability, levels of oxidative stress and antimicrobial peptide cathelicidin LL-37 and changes in the expression of surfactant proteins (SPs). Moreover, we compared A549 cell response to LPS in the presence of different serum concentrations. Additionally, the effect of N-acetylcysteine (NAC) on LPS-induced oxidative stress as a possible treatment was determined. Our results indicate that A549 cells are relatively resistant to LPS and able to maintain integrity even at high LPS concentrations. Their response to endotoxin is partially dependent on serum concentration. NAC failed to lower LPS-induced oxidative stress in A549 cells. Finally, LPS modulates SP gene expression in A549 cells in a time dependent manner and differences between short and long-term cultures were present. Our results support the idea that long-term cultivation of A549 cells could promote a more ATII-like phenotype and thus could be a more suitable model for ATII cells, especially for in vitro studies dealing with surfactant production.

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Section: Discussionmentioning

confidence: 99%

Short-Term versus Long-Term Culture of A549 Cells for Evaluating the Effects of Lipopolysaccharide on Oxidative Stress, Surfactant Proteins and Cathelicidin LL-37

Nová

Škovierová

Strnádel

et al. 2020

IJMS

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“…This 9 amino acid sequence was called peroxiredoxin 6 inhibitor peptide-2 (PIP-2); it inhibits aiPLA 2 activity and prevents the activation of NOX2 [30]. Treatment with PIP-2 has resulted in a high level of protection against lung injury in mouse models of ALI or sepsis associated with the administration of bacterial lipopolysaccharide (LPS) [31]. The purpose of the present study was to evaluate possible protection by PIP-2 against lung injury in a mouse model of VILI.…”

Section: Introductionmentioning

confidence: 99%

A Peptide Inhibitor of Peroxiredoxin 6 Phospholipase A2 Activity Significantly Protects against Lung Injury in a Mouse Model of Ventilator Induced Lung Injury (VILI)

2021

Self Cite

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Ventilator induced lung injury (VILI) is a lung injury syndrome associated with mechanical ventilation, most frequently for treatment of Acute Lung Injury (ALI), and generally secondary to the use of greater than physiologic tidal volumes. To reproduce this syndrome experimentally, C57Bl/6 mice were intubated and ventilated with low (4 mL/Kg body weight) or high (12 mL/Kg) tidal volume for 6 h. Lung parameters with low volume ventilation were unchanged from non-ventilated (control) mice. High tidal volume ventilation resulted in marked lung injury with increased neutrophils in the bronchoalveolar lavage fluid (BALF) indicating lung inflammation, increase in both protein in BALF and lung dry/wet weight indicating lung edema, increased lung thiobarbituric acid reactive substances (TBARS), and 8-isoprostanes indicating lung lipid peroxidation, and increased lung protein carbonyls indicating protein oxidation. Either intratracheal or intravenous pretreatment of mice with a 9 amino acid peptide called peroxiredoxin 6 inhibitor peptide-2 (PIP-2) significantly reduced all parameters of lung injury by ~50–80%. PIP-2 inhibits NADPH oxidase type 2 (NOX2) activation. We propose that PIP-2 does not affect the mechanically induced lung damage component of VILI but does significantly reduce the secondary inflammatory component.

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“…First, to determine whether Salusin-β plays a role in LPS-induced ALI, rats were treated with LPS via intratracheal instillation, which is a previously published method to induce ALI in animals ( 25 , 26 ). The lung tissues and BALF of rats with ALI were collected at 24 h after treatment with or without LPS.…”

Section: Resultsmentioning

confidence: 99%

Anti‑inflammatory effect of salusin‑β knockdown on LPS‑activated alveolar macrophages via NF‑κB inhibition and HO‑1 activation

Chen

Zhang

et al. 2020

Mol Med Rep

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Inflammation of alveolar macrophages is the primary pathological factor leading to acute lung injury (ALI), and NF-κB activation and HO-1 inhibition are widely involved in inflammation. Salusin-β has been reported to contribute to the progression of the inflammatory response, but whether salusin-β could regulate inflammation in lipopolysaccharide (LPS)-induced ALI remains unknown. The present study aimed to investigate the role of salusin-β in LPS-induced ALI and to uncover the potential underlying mechanisms. Sprague-Dawley rats were subjected to LPS administration, and then pathological manifestations of lung tissues, inflammatory cytokines levels in bronchoalveolar lavage fluid (BALF) and expression of salusin-β in macrophages of lung tissues were assessed. NR8383 cells with or without salusin-β knockdown were treated with LPS, and then the concentration of inflammatory cytokines, and the expression of high mobility group box-1 (HMGB1), NF-κB signaling molecules and heme oxygenase-1 (HO-1) levels were detected. The results showed that LPS caused injury of lung tissues, increased the levels of proinflammatory cytokines in BALF, and led to higher expression of salusin-β or macrophages in lung tissues of rats. In vitro experiments, LPS also upregulated salusin-β expression in NR8383 cells. Knockdown of salusin-β using short hairpin (sh)RNA inhibited the LPS-induced generation of inflammatory cytokines. LPS also enhanced HMGB1, phosphorylated (p)-IκB and p-p65 expression, but reduced HO-1 expression in both lung tissues and NR8383 cells, which were instead inhibited by the transfection of sh-salusin-β. In addition, knockdown of HO-1 using shRNA reversed the inhibitory effect of sh-salusin-β on the LPS-induced generation of inflammatory cytokines, activation of NF-κB signaling and inactivation of HO-1. In conclusion, this study suggested that knockdown of salusin-β may inhibit LPS-induced inflammation in alveolar macrophages by blocking NF-κB signaling and upregulating HO-1 expression.

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A Peptide Inhibitor of NADPH Oxidase (NOX2) Activation Markedly Decreases Mouse Lung Injury and Mortality Following Administration of Lipopolysaccharide (LPS)

Cited by 28 publications

References 52 publications

Short-Term versus Long-Term Culture of A549 Cells for Evaluating the Effects of Lipopolysaccharide on Oxidative Stress, Surfactant Proteins and Cathelicidin LL-37

Short-Term versus Long-Term Culture of A549 Cells for Evaluating the Effects of Lipopolysaccharide on Oxidative Stress, Surfactant Proteins and Cathelicidin LL-37

A Peptide Inhibitor of Peroxiredoxin 6 Phospholipase A2 Activity Significantly Protects against Lung Injury in a Mouse Model of Ventilator Induced Lung Injury (VILI)

Anti‑inflammatory effect of salusin‑β knockdown on LPS‑activated alveolar macrophages via NF‑κB inhibition and HO‑1 activation

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