Hydrogen peroxide and nitrite reduction in exhaled breath condensate of COPD patients

Stefańska, Joanna; Sarniak, Agata; Włodarczyk, Anna; Sokołowska, Milena; Doniec, Zbigniew; Białasiewicz, Piotr; Nowak, Dariusz; Pawliczak, Rafał

doi:10.1016/j.pupt.2012.06.001

Cited by 42 publications

(24 citation statements)

References 44 publications

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“…Although apocynin inhibits NOX2 assembly [51–53] and requires NOX2 to elicit protection after cerebral infarction [54], apocynin also may produce anti-inflammatory and antioxidant effects independent of NOX2 [55, 56]. Despite this mechanistic limitation, apocynin exhibits documented clinical safety in asthma and chronic obstructive pulmonary disease patients [57, 58] and reduced inflammasome formation, even when administered up to 24 hours post-TBI. As 24 hours is beyond the peak expression of NOX2 in neurons [16], the delayed NOX2 elevation in immune cells may mediate release of proinflammatory cytokines, such as IL-1 β , to exacerbate the secondary injury after TBI.…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury

Merry

Wang

Dhandapani

et al. 2017

Oxidative Medicine and Cellular Longevity

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. After the initial primary mechanical injury, a complex secondary injury cascade involving oxidative stress and neuroinflammation follows, which may exacerbate the injury and complicate the healing process. NADPH oxidase 2 (NOX2) is a major contributor to oxidative stress in TBI pathology, and inhibition of NOX2 is neuroprotective. The NLRP3 inflammasome can become activated in response to oxidative stress, but little is known about the role of NOX2 in regulating NLRP3 inflammasome activation following TBI. In this study, we utilized NOX2 knockout mice to study the role of NOX2 in mediating NLRP3 inflammasome expression and activation following a controlled cortical impact. Expression of NLRP3 inflammasome components NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC), as well as its downstream products cleaved caspase-1 and interleukin-1β (IL-1β), was robustly increased in the injured cerebral cortex following TBI. Deletion of NOX2 attenuated the expression, assembly, and activity of the NLRP3 inflammasome via a mechanism that was associated with TXNIP, a sensor of oxidative stress. The results support the notion that NOX2-dependent inflammasome activation contributes to TBI pathology.

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Section: Discussionmentioning

confidence: 99%

NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury

Merry

Wang

Dhandapani

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…or may highlight the inadequacies of mouse models. While it is not clear from earlier descriptions as to whether NOX2 represents a promising target for human drug development, apocynin administered to COPD patients was effective in decreasing H 2 O 2 levels in exhaled breath condensates (283).…”

Section: Nox2 As a Target For Drug Developmentmentioning

confidence: 92%

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Diebold

Smith

Yang

et al. 2015

Antioxidants & Redox Signaling

106

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Significance: NOX2 is important for host defense, and yet is implicated in a large number of diseases in which inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases. Recent Advances: Recent drug development programs have targeted several NOX isoforms that are implicated in a variety of diseases. The focus has been primarily on NOX4 and NOX1 rather than on NOX2, due, in part, to concerns about possible immunosuppressive side effects. Nevertheless, NOX2 clearly contributes to the pathogenesis of many inflammatory diseases, and its inhibition is predicted to provide a novel therapeutic approach. Critical Issues: Possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will contribute to increased infections and/or autoimmune disorders. The state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is also summarized. Future Directions: NOX2 inhibitors show particular promise for the treatment of inflammatory diseases, both acute and chronic. Theoretical side effects include pro-inflammatory and autoimmune complications and should be considered in any therapeutic program, but in our opinion, available data do not indicate that they are sufficiently likely to eliminate NOX2 as a drug target, particularly when weighed against the seriousness of many NOX2-related indications. Model studies demonstrating efficacy with minimal side effects are needed to encourage future development of NOX2 inhibitors as therapeutic agents. Antioxid. Redox Signal. 23,

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“…Patients with neutrophilic and mixed asthma respond poorly to corticosteroid therapy, and increased numbers of neutrophils with persistent eosinophilia are seen in severe asthma and sudden‐onset fatal asthma . In both types of complex phenotypes, other factors such as genetics, epithelial barrier dysfunction, innate immune response, environmental exposures, viral infections, and comorbidities may further modulate inflammation, bringing the stability of dominant physiopathological mechanisms to question . Therefore, better understanding of the characteristics of each inflammatory subgroup is crucial for extensive development of personalized/precision medicine .…”

Section: Introductionmentioning

confidence: 99%

Tight junction, mucin, and inflammasome‐related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice

Tan

Hagner

Ruchti

et al. 2018

Allergy

129

131

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Background: Asthma is a chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Specific pathways are thought to be involved in the pathomechanisms of different inflammatory phenotypes of asthma; however, direct in vivo comparison has not been performed. Methods:We developed mouse models representing three different phenotypes of allergic airway inflammation-eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitization and challenge. Transcriptomic analysis of the lungs, followed by the RT-PCR, western blot, and confocal microscopy, was performed. Primary human bronchial epithelial cells cultured in air-liquid interface were used to study the mechanisms revealed in the in vivo models.Results: By whole-genome transcriptome profiling of the lung, we found that airway tight junction (TJ), mucin, and inflammasome-related genes are differentially expressed in these distinct phenotypes. Further analysis of proteins from these families revealed that Zo-1 and Cldn18 were downregulated in all phenotypes, while increased Cldn4 expression was characteristic for neutrophilic airway inflammation.Mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic phenotype. Increased expression of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1, and IL-1β was characteristic for neutrophilic asthma. In addition, we showed that inflammasome/Th17/neutrophilic axis cytokine-IL-1βmay transiently impair epithelial barrier function, while IL-1β and IL-17 increase mucin expressions in primary human bronchial epithelial cells.Conclusion: Our findings suggest that differential expression of TJ, mucin, and inflammasome-related molecules in distinct inflammatory phenotypes of asthma may be linked to pathophysiology and might reflect the differences observed in the clinic. K E Y W O R D Sendotype, epithelial barrier, house dust mite, phenotype, precision medicine Tan and Hagner equal first-author contribution.

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Hydrogen peroxide and nitrite reduction in exhaled breath condensate of COPD patients

Cited by 42 publications

References 44 publications

NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury

NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Tight junction, mucin, and inflammasome‐related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice

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