Acid aspiration-induced lung inflammation and injury are exacerbated in NADPH oxidase-deficient mice

Segal, Brahm H.; Davidson, Bruce A.; Hutson, Alan D.; Russo, Thomas A.; Holm, Bruce A.; Mullan, Barbara A.; Habitzruther, Michael; Holland, Steven M.; Knight, Paul R.

doi:10.1152/ajplung.00281.2006

Cited by 44 publications

(46 citation statements)

References 39 publications

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“…Some studies have implicated ROS as a key element in the pathogenesis of ALI/ARDS following gastric content aspiration in mouse models [100], but to date, only one has demonstrated the role of NOX enzyme in this context. Indeed, exposure of p47 phox -deficient mice to HCl leads to increased pulmonary neutrophilic infiltration, alveolarcapillary barrier leakage, and enhanced level of proinflammatory cytokine compared to WT mice [101], suggesting a protective role of NOX2 in HCl-induced lung injury by modulating the inflammatory response.…”

Section: Epithelium and Endothelium Targetsmentioning

confidence: 99%

NOX enzymes: potential target for the treatment of acute lung injury

Carnesecchi¹,

Pache²,

Barazzone-Argiroffo³

2012

Cell. Mol. Life Sci.

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Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), is characterized by acute inflammation, disruption of the alveolarcapillary barrier, and in the organizing stage by alveolar pneumocytes hyperplasia and extensive lung fibrosis. The cellular and molecular mechanisms leading to the development of ALI/ARDS are not completely understood, but there is evidence that reactive oxygen species (ROS) generated by inflammatory cells as well as epithelial and endothelial cells are responsible for inflammatory response, lung damage, and abnormal repair. Among all ROS-producing enzymes, the members of NADPH oxidases (NOXs), which are widely expressed in different lung cell types, have been shown to participate in cellular processes involved in the maintenance of lung integrity. It is not surprising that change in NOXs' expression and function is involved in the development of ALI/ARDS. In this context, the use of NOX inhibitors could be a possible therapeutic perspective in the management of this syndrome. In this article, we summarize the current knowledge concerning some cellular aspects of NOXs localization and function in the lungs, consider their contribution in the development of ALI/ARDS and discuss the place of NOX inhibitors as potential therapeutical target.

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Section: Epithelium and Endothelium Targetsmentioning

confidence: 99%

NOX enzymes: potential target for the treatment of acute lung injury

Carnesecchi¹,

Pache²,

Barazzone-Argiroffo³

2012

Cell. Mol. Life Sci.

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“…Genetic mutations in NOX2 (gp91phox), p47phox, p67phox and p22phox are known to be responsible for development of CGD, but minimal evidence exists for associations of these polymorphisms with other diseases, and a recent analysis failed to show an association of polymorphisms within gp91phox, p47phox, p67phox or p22phox with infectious or non-infectious lung diseases, such as tuberculosis or sarcoidosis (199). Attempts to implicate NOX2 or p47phox in models of lung inflammation and injury, using gp91phox−/− or p47phox−/− mice, demonstrated that genetic NADPH oxidase deficiency was in many cases associated with enhanced inflammation and injury (200)(201)(202)(203), implicating that NOX2 also has beneficial functions in regulating inflammatoryimmune responses. For example, infection of gp91phox−/− mice with the yeast C. neoformans or with influenza virus was in either case found to result in increased Th1-skewed inflammation and granuloma formation, compared to their wild-type counterparts, which led to increased influenza clearance and protection against C. neoformans infection (204,205).…”

Section: Nox2mentioning

confidence: 99%

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Vliet

2008

Free Radical Biology and Medicine

187

192

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The deliberate production of reactive oxygen species (ROS) by phagocyte NADPH oxidase is widely appreciated as a critical component of antimicrobial host defense. Recently, additional homologs of NADPH oxidase (NOX) have been discovered throughout the animal and plant kingdoms, which appear to possess diverse functions in addition to host defense, including cell proliferation, differentiation, and regulation of gene expression. Several of these NOX homologs are also expressed within the respiratory tract, where they participate in innate host defense as well as in epithelial and inflammatory cell signaling and gene expression, and fibroblast and smooth muscle cell proliferation, in response to bacterial or viral infection and environmental stress. Inappropriate expression or activation of NOX/DUOX during various lung pathologies suggests their specific involvement in respiratory disease. This review summarizes the current state of knowledge regarding the general functional properties of mammalian NOX enzymes, and their specific importance in respiratory tract physiology and pathology.

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“…Deficiency of NOX2 in humans results in chronic granulomatous disease characterized by multiple abscess formation due to the inability of bacterial pathogens to be removed. However, in animal studies of chronic injury, NOX deficiency was associated with enhanced inflammation and subsequent tissue damage [9][10][11][12][13], implying that NOX2 also has beneficial functions in immune responses and cell signaling. Several studies have demonstrated that the superoxide generated by NOX2 is a key step in the development of endothelial cell dysfunction and functions by altering vascular tone and modulating cell signaling pathways [14][15][16][17].…”

Section: Superoxidementioning

confidence: 99%

Tipping the redox balance of oxidative stress in fibrogenic pathways in chronic kidney disease

Okamura

Himmelfarb

2009

Pediatr Nephrol

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Patients with moderate to advanced chronic kidney disease or end-stage renal disease have a greatly increased cardiovascular risk that cannot be explained entirely by traditional cardiovascular risk factors. An increase in oxidative stress and inflammation have been proposed as nontraditional cardiovascular risk factors in this patient population. Oxidative stress reflects the redox balance between oxidant generation and antioxidant mechanisms. The generation of reactive oxygen species is not simply a random process that oxidizes nearby macromolecules, but, in many instances, the oxidants target particular amino acid residues or lipid moieties. Oxidant mechanisms are now recognized to be intimately involved in cell signaling and to be vital components of the immune response. This is equally true for antioxidant mechanisms as well. In the progression of chronic kidney disease, the redox balance is not in equilibrium and is tipped toward oxidation, resulting in the dysregulation of cellular process and subsequent tissue injury. In this review we discuss the major oxidant and antioxidant pathways and the biomarkers to assess redox status. We also review the data linking the pathogenesis of oxidative stress, inflammation, and the progressive loss of kidney function in chronic kidney disease.

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Acid aspiration-induced lung inflammation and injury are exacerbated in NADPH oxidase-deficient mice

Abstract: SM, Knight PR 3rd. Acid aspiration-induced lung inflammation and injury are exacerbated in NADPH oxidase-deficient mice.

Cited by 44 publications

References 39 publications

NOX enzymes: potential target for the treatment of acute lung injury

NOX enzymes: potential target for the treatment of acute lung injury

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Tipping the redox balance of oxidative stress in fibrogenic pathways in chronic kidney disease

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