NADPH Oxidase-1 Plays a Crucial Role in Hyperoxia-induced Acute Lung Injury in Mice

Carnesecchi, Stéphanie; Deffert, Christine; Pagano, Alessandra; Garrido‐Urbani, Sarah; Métrailler-Ruchonnet, Isabelle; Schäppi, Michela; Donati, Yves; Matthay, Michael A.; Krause, Karl‐Heinz; Argiroffo, Constance Barazzone

doi:10.1164/rccm.200902-0296oc

Cited by 135 publications

(145 citation statements)

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“…In addition, it has been shown that ROS can disrupt intercellular tight junctions of the endothelium by phosphorylation of focal adhesion kinase [41]. Hence, deficiency or blockade of reduced nicotinamide adenine dinucleotide phosphate oxidase prevents ALI [38,42,43]. However, in our study, pioglitazone failed to affect ROS release.…”

Section: Discussioncontrasting

confidence: 74%

“…The in vivo importance of neutrophil elastase in ALI is further corroborated in studies using elastase-deficient mice [36] or employing specific inhibitors [37]. Although the release of ROS is an important antimicrobial mechanism, overproduction of ROS can cause tissue damage in sepsis and ALI [38]. In animal models of ALI, neutrophil-derived ROS cause lung injury, as shown by histological examination and permeability measurements [39,40].…”

Section: Discussionmentioning

confidence: 99%

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Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

2012

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Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Activation and recruitment of neutrophils are regarded as key mechanisms in the progression of ALI. As pioglitazone holds potent pleiotropic anti-inflammatory effects, we explored its effects during ALI.C57Bl/6 mice were exposed to aerosolised lipopolysaccharides (LPSs) (500 mg?mL) and their alveolar, interstitial and intravascular neutrophils were assessed 4 h later. Lung permeability changes were evaluated by fluorescein isothiocyanate-dextran clearance and protein content in the bronchoalveolar lavage fluid. In vitro, human isolated neutrophils were pretreated with piolitazone (10 mM, for 1 or 3 h) and then activated with N-formyl-L-methionyl-L-leucyl-Lphenylalanine. Neutrophil activation, adhesion, release and formation of reactive oxygen species (ROS) and phagocytosis were measured thereafter.Pioglitazone treatment before or after induction of ALI significantly diminished alveolar (reduction by 73% and 67%, respectively) and interstitial neutrophil influx (reduction by 55% and 63%, respectively) and reduced lung permeability changes (reduction by 64% and 58%, respectively) indicating a protective role of pioglitazone treatment in ALI. Moreover, pioglitazone significantly reduced degranulation and adhesion of neutrophils without affecting ROS formation and release or bacterial phagocytosis.Pioglitazone reduces recruitment and activation of neutrophils thereby preventing LPS-induced ALI. Our results imply a potential role for pioglitazone treatment in the management of ALI.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

2012

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“…Hyperoxia enhances the production of reactive oxygen species (3,12), leading to DNA strand breaks, chromosomal aberrations (5,40), and inhibition of cell cycle progression in the lung (7,54). In the neonatal period, this injury could have long-lasting consequences, because alveolarization continues for several weeks postnatally (48).…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Inflammation Modulate Rev-erbα Signaling in the Neonatal Lung and Affect Circadian Rhythmicity

Guang

Wright

Hinson

et al. 2014

Antioxidants & Redox Signaling

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Aims: The response to oxidative stress and inflammation varies with diurnal rhythms. Nevertheless, it is not known whether circadian genes are regulated by these stimuli. We evaluated whether Rev-erba, a key circadian gene, was regulated by oxidative stress and/or inflammation in vitro and in a mouse model. Results: A unique sequence consisting of overlapping AP-1 and nuclear factor kappa B (NFjB) consensus sequences was identified on the mouse Rev-erba promoter. This sequence mediates Rev-erba promoter activity and transcription in response to oxidative stress and inflammation. This region serves as an NrF2 platform both to receive oxidative stress signals and to activate Rev-erba, as well as an NFjB-binding site to repress Rev-erba with inflammatory stimuli. The amplitude of the rhythmicity of Rev-erba was altered by pre-exposure to hyperoxia or disruption of NFjB in a cell culture model of circadian simulation. Oxidative stress overcame the inhibitory effect of NFjB binding on Rev-erba transcription. This was confirmed in neonatal mice exposed to hyperoxia, where hyperoxiainduced lung Rev-erba transcription was further increased with NFjB disruption. Interestingly, this effect was not observed in similarly exposed adult mice. Innovation: These data provide novel mechanistic insights into how key circadian genes are regulated by oxidative stress and inflammation in the neonatal lung. Conclusion: Rev-erba transcription and circadian oscillation are susceptible to oxidative stress and inflammation in the neonate. Due to Rev-erba's role in cellular metabolism, this could contribute to lung cellular function and injury from inflammation and oxidative stress. Antioxid. Redox Signal. 21, 17-32.

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“…For example, by suppressing JNK signal pathways, neuropeptide substance P can promote type II alveolar epithelial cell proliferation, inhibit apoptosis after hyperoxia exposure, and attenuate hyperoxia-induced oxidative stress damage (66). Furthermore, Carnesecchi et al (67) reported that hyperoxia led to phosphorylation of JNK and ERK, two MAPKs involved in cell death signaling. In contrast, hyperoxia-induced lung injury was significantly prevented in NOX1-deficient mice, in which JNK phosphorylation was blunted and ERK phosphorylation was decreased.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

Zhao¹,

Zhou²,

Haddad

2011

Journal of Biological Chemistry

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It is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMPs) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e.g. Diptericin) allows wild-type flies to survive much better in hyperoxia. In this study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with AMP overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS levels after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that 1) AMPs play an important role in tolerance to oxidant stress, 2) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and 3) this change in redox balance plays an important role in survival in hyperoxia.Oxygen is essential for aerobic life. However, except for the beneficial role in wound healing, too little or too much oxygen can induce morbidity and mortality (1, 2). Mammalian aging and numerous diseases such as neurodegenerative diseases and chronic inflammatory diseases, as well as injury to the heart, lungs, retina, brain, and other organs due to ischemia and reperfusion states, result, by and large, from oxidant injury (3-6). High O 2 -induced oxidant injury could occur in cells in every organ, especially in the lungs, retina, heart, and brain (7,8). Prolonged exposure to high O 2 generates excessive reactive oxygen species (ROS), 2 induces cell death and oxidative stress responses, affects the immune response and DNA integrity, and modulates cell growth (5, 9 -11).Drosophila melanogaster has similar O 2 response pathways as mammals, and research on flies has enhanced our understanding of oxidant stress (12)(13)(14). In the past, through an experimental selection design over many generations, we have successfully generated D. melanogaster flies that tolerate tremendously high O 2 -induced oxidative stress. Microarray analysis has revealed that the family of antimicrobial peptides (AMPs) is over-represented among the up-regulated genes in these tolerant flies. We have further demonstrated that overexpression of even one AMP gene at a time (e.g. Diptericin (Dpt)) allows wild-type flies to survive much better in hyperoxia (15). To our knowledge, this is t...

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NADPH Oxidase-1 Plays a Crucial Role in Hyperoxia-induced Acute Lung Injury in Mice

Cited by 135 publications

References 52 publications

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

Oxidative Stress and Inflammation Modulate Rev-erbα Signaling in the Neonatal Lung and Affect Circadian Rhythmicity

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

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