The Complicated Role of Nuclear Factor Erythroid-Derived 2-Like 2 in Allergy and Asthma

Rockwell, Cheryl E.; Jin, Yining; Boss, Allison; Kaiser, Luca M; Awali, Saamera

doi:10.1124/dmd.121.000414

Cited by 10 publications

(6 citation statements)

References 103 publications

(115 reference statements)

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“…Another study has also reported impaired hematopoiesis in mouse BM following a 2 week exposure to PM 2.5 at doses of 20 and 160 μg/kg·d . Reportedly, NRF2 mediates the enhancement of PM 2.5 -induced pulmonary responses or damage, ,,− displaying a ROS-independent NRF2 regulating pathway. Our results unveiled novel mechanisms responsible for NRF2-dependent enhancement of pulmonary dysfunction and injury.…”

Section: Resultsmentioning

confidence: 94%

PM_2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice

Wang

Jin

et al. 2023

Environ. Sci. Technol.

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Although PM2.5 (fine particles with aerodynamic diameter <2.5 μm) exposure shows the potential to impact normal hematopoiesis, the detailed alterations in systemic hematopoiesis and the underlying mechanisms remain unclear. For hematopoiesis under steady-state or stress conditions, nuclear factor erythroid 2-related factor 2 (NRF2) is essential for regulating hematopoietic processes to maintain blood homeostasis. Herein, we characterized changes in the populations of hematopoietic stem progenitor cells and committed hematopoietic progenitors in the lungs and bone marrow (BM) of wild-type and Nrf2 –/– C57BL/6J male mice. PM2.5-induced NRF2-dependent biased hematopoiesis toward myeloid lineage in the lungs and BM generates excessive numbers of various inflammatory immune cells, including neutrophils, monocytes, and platelets. The increased population of these immune cells in the lungs, BM, and peripheral blood has been associated with observed pulmonary fibrosis and high disease risks in an NRF2-dependent manner. Therefore, although NRF2 is a protective factor against stressors, upon PM2.5 exposure, NRF2 is involved in stress myelopoiesis and enhanced PM2.5 toxicity in pulmonary injury, even leading to systemic inflammation.

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Section: Resultsmentioning

confidence: 94%

PM_2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice

Wang

Jin

et al. 2023

Environ. Sci. Technol.

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“…The anti-inflammatory effects of Nrf2 have been reported in numerous disease models, including asthma ( 64 ). Rangasamy et al ( 15 ) reported that Nrf2 knockout mice were more susceptible to asthma, and Sussan et al ( 16 ) reported the role of Nrf2 in the cytoprotective effect on the airway epithelia of subjects with asthma.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates airway inflammation and oxidative stress in asthma via the Nrf2 signaling pathway

et al. 2022

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Allergic asthma is a chronic inflammatory disease in which oxidative stress serves a pivotal role. In clinical practice, dexmedetomidine (DEX), an α-2-adrenergic receptor agonist, is used as a sedative. DEX exhibits antioxidative and organ-protective properties. In a murine model of asthma, DEX has a therapeutic effect via the toll like receptor 4/NF-кB signaling pathway; however, whether DEX can exert an antioxidative effect on asthma has yet to be elucidated. In the present study, a T helper (Th)2-dominant murine asthma model was established. DEX treatment significantly reduced eosinophilic airway inflammation, mucus overproduction and airway hyperresponsiveness, as well as the concentrations of Th2 cytokines. The lung tissues of mice with asthma were characterized by redox imbalance (increased oxidative stress and impaired antioxidant capacity). DEX treatment alleviated this imbalance by decreasing the levels of malondialdehyde and reactive oxygen species, and increasing the levels of glutathione. Furthermore, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was inhibited in the lung tissues of asthmatic mice; these effects were noted in its downstream genes, heme oxygenase 1 and glutathione peroxidase 4. In mice with asthma, DEX treatment induced the expression of these antioxidant genes and the activation of Nrf2, whereas ML385 (an inhibitor of Nrf2) partially abrogated the antioxidative and therapeutic effects of DEX. To the best of our knowledge, the present study is the first to demonstrate the protective effect of DEX on Th2-dominant asthma through the activation of the Nrf2 signaling pathway. The results suggested that the antioxidative properties of DEX could be beneficial in clinical application of DEX for the relief of asthmatic symptoms.

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“…9 Nrf2 is one of the most important transcription factors in the cellular response to oxidative stress. 10 Several studies have confirmed that Nrf2 is one of the target proteins of AKT, and either AKT or its upstream PI3K inhibitors can inhibit Nrf2 activity. The aim of this experiment was to investigate the effect of PI3K/Akt activation of Nrf2 on oxidative stress and airway inflammation in AA.…”

Section: Introductionmentioning

confidence: 99%

Modified Haoqin Qingdan Decoction Exerts Antioxidant Effect via Activating PI3K/Akt/Nrf2 Pathway on Allergic Asthma Mice

Dong,

Zhang,

et al. 2024

Natural Product Communications

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Objective The aim of this study was to investigate the antioxidant effect and potential mechanism of Modified Haoqin Qingdan Decoction on ovalbumin (OVA)-induced allergic asthma (AA) mice. Methods The AA model of mice was induced by OVA combined with aluminum hydroxide. Resistance Index (RI) in airway was analyzed by AniRes2005 animal pulmonary function analyzer. H&E staining was used to evaluate the pathological changes of lung tissue. The apoptosis in lung tissue was detected by TUNEL staining. The percentage of EOS cells in bronchoalveolar lavage fluid was determined by flow cytometry. The levels of IL-1β, IL-6, IL-4, GM-CSF, TNF-α, and IFN-γ in serum were determined by ELISA. Biochemical kits were used to detect levels of SOD, MDA, and GSH-Px in lung tissue. The protein expression of PI3K, p-PI3K, Akt, p-Akt, and nucleoprotein Nrf-2 in lung tissue was detected by western blotting. Result Modified Haoqin Qingdan Decoction reduced RI, alleviated the degree of histopathological damage, inhibited apoptosis rate, reduced the proportion of EOS cells, downregulated IL-1β, IL-6, IL-4, GM-CSF, TNF-α, IFN-γ, and MDA, upregulated SOD, GSH-Px, p-PI3K, p-Akt, and nucleoprotein Nrf-2. Conclusion Modified Haoqin Qingdan Decoction activated nucleoprotein Nrf2 by regulating the PI3K/Akt signaling pathway to exert its protective effect against inflammatory and oxidative stress in AA mice.

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The Complicated Role of Nuclear Factor Erythroid-Derived 2-Like 2 in Allergy and Asthma

Cited by 10 publications

References 103 publications

PM_2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice

PM_2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice

Dexmedetomidine attenuates airway inflammation and oxidative stress in asthma via the Nrf2 signaling pathway

Modified Haoqin Qingdan Decoction Exerts Antioxidant Effect via Activating PI3K/Akt/Nrf2 Pathway on Allergic Asthma Mice

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The Complicated Role of Nuclear Factor Erythroid-Derived 2-Like 2 in Allergy and Asthma

Cited by 10 publications

References 103 publications

PM2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice

PM2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice

Dexmedetomidine attenuates airway inflammation and oxidative stress in asthma via the Nrf2 signaling pathway

Modified Haoqin Qingdan Decoction Exerts Antioxidant Effect via Activating PI3K/Akt/Nrf2 Pathway on Allergic Asthma Mice

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PM_2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice

PM_2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice