Mucosal Reactive Oxygen Species Are Required for Antiviral Response: Role of Duox in Influenza A Virus Infection

Strengert, Monika; Jennings, Richard; Davanture, Suzel; Hayes, Patti; Gabriel, Gülşah; Knaus, Ulla G.

doi:10.1089/ars.2013.5353

Cited by 80 publications

(87 citation statements)

References 64 publications

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“…ROS, such as superoxide anions, H 2 O 2 , and hydroxyl radicals, are ubiquitous, highly reactive, diffusible molecules (16,28). It has long been recognized that ROS cause complex and irreversible damage to cellular constituents that impairs cellular homeostasis (15).…”

Section: Discussionmentioning

confidence: 99%

Caffeic acid improves cell viability and protects against DNA damage: involvement of reactive oxygen species and extracellular signal-regulated kinase

Chen

Jiang

et al. 2015

Braz J Med Biol Res

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Hormesis is an adaptive response to a variety of oxidative stresses that renders cells resistant to harmful doses of stressing agents. Caffeic acid (CaA) is an important antioxidant that has protective effects against DNA damage caused by reactive oxygen species (ROS). However, whether CaA-induced protection is a hormetic effect remains unknown, as is the molecular mechanism that is involved. We found that a low concentration (10 μM) of CaA increased human liver L-02 cell viability, attenuated hydrogen peroxide (H2O2)-mediated decreases in cell viability, and decreased the extent of H2O2-induced DNA double-strand breaks (DSBs). In L-02 cells exposed to H2O2, CaA treatment reduced ROS levels, which might have played a protective role. CaA also activated the extracellular signal-regulated kinase (ERK) signal pathway in a time-dependent manner. Inhibition of ERK by its inhibitor U0126 or by its specific small interfering RNA (siRNA) blocked the CaA-induced improvement in cell viability and the protective effects against H2O2-mediated DNA damage. This study adds to the understanding of the antioxidant effects of CaA by identifying a novel molecular mechanism of enhanced cell viability and protection against DNA damage.

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Section: Discussionmentioning

confidence: 99%

Caffeic acid improves cell viability and protects against DNA damage: involvement of reactive oxygen species and extracellular signal-regulated kinase

Chen

Jiang

et al. 2015

Braz J Med Biol Res

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“…An intriguing finding is that, DUOX2, which is highly expressed in airway epithelial cells and is the major source of H 2 O 2 by these cells, like NOX1, appears to protect the host from influenza A virus infections. DUOX2 activity was associated with a marked reduction in influenza replication within epithelial cells, resulting in protection in the early phases of infection (Strengert et al, 2014). Overall, it appears that ROS have contrasting roles on influenza virus infections, depending on the cell type they are generated within.…”

Section: Dbnp366mentioning

confidence: 98%

“…However, it is noteworthy that there is an emergence of literature that indicates ROS as possessing important antiviral effects against influenza viruses. In fact, the key study by (Strengert et al, 2014) showed that H 2 O 2 suppresses virus replication and release of virus by airway epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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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“…At indicated time points, bronchoalveolar lavage (BAL) was analyzed for cytokines using the multiplex-fluorokine assay (R&D Systems), for NET formation by Sytox Green (5 mM) fluorometry, for type I IFNs, and for virus load as described. [25][26][27] Paraffin-embedded lung sections were stained with hematoxylin and eosin or modified Carstairs, and visualized with a Leica DFC300X camera and IM50 imaging software.…”

Section: In Vivo Lung Modelsmentioning

confidence: 99%

RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

Jennings¹,

Strengert²,

Hayes³

et al. 2014

Blood

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Mucosal Reactive Oxygen Species Are Required for Antiviral Response: Role of Duox in Influenza A Virus Infection

Abstract: Duox-derived ROS are host protective and essential for counteracting IAV replication.

Cited by 80 publications

References 64 publications

Caffeic acid improves cell viability and protects against DNA damage: involvement of reactive oxygen species and extracellular signal-regulated kinase

Caffeic acid improves cell viability and protects against DNA damage: involvement of reactive oxygen species and extracellular signal-regulated kinase

NADPH Oxidases as Novel Pharmacologic Targets against Influenza A Virus Infection

RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

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