Oxidative Stress Is an Important Component of Airway Inflammation in Mice Exposed to Cigarette Smoke or Lipopolysaccharide

Lagente, Vincent; Planquois, Jean-Michel; Leclerc, Olivier; Schmidlin, Fabien; Bertrand, Claude

doi:10.1111/j.1440-1681.2007.04848.x

Cited by 35 publications

(30 citation statements)

References 28 publications

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“…In one study (150), the number of macrophages and neutrophils and levels of IL-6, keratinocyte-derived chemokine (KC/CXCL1), and MCP1/ CCL2 in BALF were lower in p47phox…”

Section: Nox2 As a Target For Drug Developmentmentioning

confidence: 94%

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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“…In one study (150), the number of macrophages and neutrophils and levels of IL-6, keratinocyte-derived chemokine (KC/CXCL1), and MCP1/ CCL2 in BALF were lower in p47phox…”

Section: Nox2 As a Target For Drug Developmentmentioning

confidence: 94%

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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“…The lung responses in p47phox-and NOX2-null mice were associated with increased production of proinflammatory cytokines and chemokines via a TLR4-NF-kB pathway, indicating that NOX2 may mediate anti-inflammatory functions by restraining TLR4 activation (Yao et al, 2008). However, another group reported that p47phox-null mice have less inflammation, IL-6, keratinocytederived chemokine, and monocyte chemoattractant protein-1 in lung-lavage specimens after cigarette-smoke exposure compared with wild-type mice (Lagente et al, 2008). The differences observed by these groups may be due to variability in lung compartment sampling, cellular distributions, and chronicity of cigarette-smoke exposure.…”

Section: Dbnp366mentioning

confidence: 95%

NADPH Oxidases as Novel Pharmacologic Targets against Influenza A Virus Infection

Vlahos¹,

Selemidis²

2014

Mol Pharmacol

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Influenza A viruses represent a major global health care challenge, with imminent pandemics, emerging antiviral resistance, and long lag times for vaccine development, raising a pressing need for novel pharmacologic strategies that ideally target the pathology irrespective of the infecting strain. Reactive oxygen species (ROS) pervade all facets of cell biology with both detrimental and protective properties. Indeed, there is compelling evidence that activation of the NADPH oxidase 2 (NOX2) isoform of the NADPH oxidase family of ROS-producing enzymes promotes lung oxidative stress, inflammation, injury, and dysfunction resulting from influenza A viruses of low to high pathogenicity, as well as impeding virus clearance. By contrast, the dual oxidase isoforms produce ROS that provide vital protective antiviral effects for the host. In this review, we propose that inhibitors of NOX2 are better alternatives than broad-spectrum antioxidant approaches for treatment of influenza pathologies, for which clinical efficacy may have been limited owing to poor bioavailability and inadvertent removal of beneficial ROS. Finally, we briefly describe the current suite of NADPH oxidase inhibitors and the molecular features of the NADPH oxidase enzymes that could be exploited by drug discovery for development of more specific and novel inhibitors to prevent or treat disease caused by influenza.

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“…Therefore, the biological function of NADPH oxidase enzymes might be attributable to the production of ROS. 31 ROS have been shown to mediate the expression of VCAM-1 and ICAM-1. 8 Most of TNF-␣ actions are elicited by TNFR1, which contains a death domain that fosters protein-protein interactions, particularly with other death-domain proteins.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of HO-1 Protects against TNF-α-Mediated Airway Inflammation by Down-Regulation of TNFR1-Dependent Oxidative Stress

Lee

Luo

Lee

et al. 2009

The American Journal of Pathology

160

151

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Oxidative stresses are believed to play an important role in the induction of both cell adhesion molecules and pro-inflammatory cytokines, a key event in a variety of inflammatory processes. The enzyme heme oxygenase-1 (HO-1) functions as an antioxidant and serves to protect against tissue injury. In this study, we report that HO-1 was induced in cultured human tracheal smooth muscle cells after either treatment with a potent inducer of HO-1 activity, cobalt protoporphyrin IX, or infection with a recombinant adenovirus that carries the human HO-1 gene. Overexpression of HO-1 protected against tumor necrosis factor (TNF)-␣-mediated airway inflammation via the down-regulation of oxidative stress, adhesion molecules, and interleukin-6 in both cultured human tracheal smooth muscle cells and the airways of mice. In addition, HO-1 overexpression inhibited TNF-␣-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, adherence of THP-1 cells, generation of interleukin-6, p47 phox translocation, and nuclear factor-B activation. HO-1 overexpression also attenuated TNF-␣-induced oxidative stress, which was abrogated in the presence of both the HO-1 inhibitor, zinc protoporphyrin IX, as well as a carbon monoxide scavenger. In addition, HO-1 overexpression reduced the formation of a TNFR1/c-Src/p47 phox complex. These results suggest that HO-1 functions as a suppressor of TNF-␣ signaling, not only by inhibiting the expression of adhesion molecules and generation of interleukin-6, but also by diminishing intracellular reactive oxygen species production and nuclear factor-B activation in both cultured human tracheal smooth muscle cells and the airways of mice.

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Oxidative Stress Is an Important Component of Airway Inflammation in Mice Exposed to Cigarette Smoke or Lipopolysaccharide

Cited by 35 publications

References 28 publications

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

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

NADPH Oxidases as Novel Pharmacologic Targets against Influenza A Virus Infection

Overexpression of HO-1 Protects against TNF-α-Mediated Airway Inflammation by Down-Regulation of TNFR1-Dependent Oxidative Stress

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