DUOX1 in mammalian disease pathophysiology

Ashtiwi, Nuha Milad; Sarr, Demba; Rada, Balázs

doi:10.1007/s00109-021-02058-2

Cited by 12 publications

(8 citation statements)

References 108 publications

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“…While Duox1 was discovered in 2000 (2) and its role in OSCN − generation and LPO partnership was proposed in 2003 (3), this study demonstrates the antimicrobial function of Duox1 in vivo. Prior in vivo studies reported associations of Duox1 with the pathogeneses of several diseases including allergic asthma and chronic obstructive pulmonary disease and with the function of uroepithelial cells (1,(46)(47)(48). Our study identifies the in vivo physiological role of Duox1 and shows that Duox1 activity is beneficial to the host response against viral infection.…”

Section: Discussionmentioning

confidence: 54%

Dual oxidase 1 promotes antiviral innate immunity

Sarr

Gingerich

Asthiwi

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Dual oxidase 1 (DUOX1) is an NADPH oxidase that is highly expre-ssed in respiratory epithelial cells and produces H2O2 in the airway lumen. While a line of prior in vitro observations suggested that DUOX1 works in partnership with an airway peroxidase, lactoperoxidase (LPO), to produce antimicrobial hypothiocyanite (OSCN−) in the airways, the in vivo role of DUOX1 in mammalian organisms has remained unproven to date. Here, we show that Duox1 promotes antiviral innate immunity in vivo. Upon influenza airway challenge, Duox1−/− mice have enhanced mortality, morbidity, and impaired lung viral clearance. Duox1 increases the airway levels of several cytokines (IL-1β, IL-2, CCL1, CCL3, CCL11, CCL19, CCL20, CCL27, CXCL5, and CXCL11), contributes to innate immune cell recruitment, and affects epithelial apoptosis in the airways. In primary human tracheobronchial epithelial cells, OSCN− is generated by LPO using DUOX1-derived H2O2 and inactivates several influenza strains in vitro. We also show that OSCN− diminishes influenza replication and viral RNA synthesis in infected host cells that is inhibited by the H2O2 scavenger catalase. Binding of the influenza virus to host cells and viral entry are both reduced by OSCN− in an H2O2-dependent manner in vitro. OSCN− does not affect the neuraminidase activity or morphology of the influenza virus. Overall, this antiviral function of Duox1 identifies an in vivo role of this gene, defines the steps in the infection cycle targeted by OSCN−, and proposes that boosting this mechanism in vivo can have therapeutic potential in treating viral infections.

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Section: Discussionmentioning

confidence: 54%

Dual oxidase 1 promotes antiviral innate immunity

Sarr

Gingerich

Asthiwi

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…It is well-known that heart failure development is associated with oxidative stress, which might be caused by the complex effects of ROS [ 4 ]. DUOX1-induced ROS production has also been shown in various diseases, such as DUOX1 nasal polyposis, allergy and asthma, chronic obstructive pulmonary disease, lung fibrosis and cancer [ 30 ]. Consistent with these reports, we found that the increased ROS production were associated with DUOX1 expression.…”

Section: Discussionmentioning

confidence: 99%

Upregulated dual oxidase 1-induced oxidative stress and caspase-1-dependent pyroptosis reflect the etiologies of heart failure

Li,

Xia,

Chen

et al. 2024

BMC Mol and Cell Biol

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Background Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure. Materials and methods AC16 cells were treated with 2 µmol/L of doxorubicin (DOX) for 12, 24, and 48 h to construct a heart failure model. DUOX1 overexpression and silencing in AC16 cell were established. DUOX1 expression was detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pyroptosis and reactive oxygen species (ROS) production were measured by flow cytometry. Results Increased DUOX1 expression levels were observed after DOX treatment for 24 h in AC16 cells. DUOX1 silencing inhibited DOX-induced pyroptosis and ROS production. The release of IL-1β, IL-18, and lactate dehydrogenase (LDH), and expression levels of pyroptosis-related proteins were also decreased. DUOX1 overexpression increased pyroptosis, ROS production, IL-1β, IL-18, and LDH release, and pyroptosis-related protein expression. N-acetyl-cysteine (NAC) significantly reversed DUOX1-induced pyroptosis, ROS, and related factors. Conclusion These results suggest that DUOX1-derived genotoxicity could promote heart failure development. In the process, oxidative stress and pyroptosis may be involved in the regulation of DUOX1 in heart failure.

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“…Among several genes exhibiting significant upregulation at multiple time points, dual oxidase 1 ( Duox1 ) demonstrated the most pronounced increase. Duox1 is a member of the NADPH oxidative enzyme family that generates ROS upon binding of calcium ions ( 68 ) Initially identified in the mammalian thyroid gland and referred to as thyroid oxidase ( 69 ), Duox1 is expressed in various tissues, including the lung, placenta, liver, urothelial cells, and the brain ( 70 , 71 ). Although Duox1 expression has been identified in retinal ganglion cells ( 72 ), its presence in somatic ganglia has not been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Forced swim stress exacerbates inflammation-induced hyperalgesia and oxidative stress in the rat trigeminal ganglia

Ro,

Zhang,

Asgar

et al. 2024

Front. Pain Res.

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This study investigates the impact of combining psychophysical stress, induced by forced swim (FSS), with masseter inflammation on reactive oxygen species (ROS) production in trigeminal ganglia (TG), TRPA1 upregulation in TG, and mechanical hyperalgesia. In a rat model, we demonstrate that FSS potentiates and prolongs CFA-induced ROS upregulation within TG. The ROS levels in CFA combined with FSS group surpass those in the CFA-only group on days 4 and 28 post-treatment. FSS also enhances TRPA1 upregulation in TG, with prolonged expression compared to CFA alone. Furthermore, CFA-induced mechanical hyperalgesia is significantly prolonged by FSS, persisting up to day 28. PCR array analyses reveal distinct alterations in oxidative stress genes under CFA and CFA combined with FSS conditions, suggesting an intricate regulation of ROS within TG. Notably, genes like Nox4, Hba1, Gpx3, and Duox1 exhibit significant changes, providing potential targets for managing oxidative stress and inflammatory pain. Western blot and immunohistochemistry confirm DUOX1 protein upregulation and localization in TG neurons, indicating a role in ROS generation under inflammatory and stress conditions. This study underscores the complex interplay between psychophysical stress, inflammation, and oxidative stress in the trigeminal system, offering insights into novel therapeutic targets for pain management.

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DUOX1 in mammalian disease pathophysiology

Cited by 12 publications

References 108 publications

Dual oxidase 1 promotes antiviral innate immunity

Dual oxidase 1 promotes antiviral innate immunity

Upregulated dual oxidase 1-induced oxidative stress and caspase-1-dependent pyroptosis reflect the etiologies of heart failure

Forced swim stress exacerbates inflammation-induced hyperalgesia and oxidative stress in the rat trigeminal ganglia

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