Quercetin prevents rhinovirus-induced progression of lung disease in mice with COPD phenotype

Farazuddin, Mohammad; Mishra, Rahul; Jing, Yaxun; Srivastava, Vikram; Comstock, Adam T.; Sajjan, Uma S.

doi:10.1371/journal.pone.0199612

Cited by 61 publications

(68 citation statements)

References 37 publications

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“…Previously, we demonstrated that COPD airway epithelial cells show exaggerated type I and type III IFN expression in response to RV infection (3), and this was not associated with augmented viral clearance. Similarly, mice displaying COPD-like lung disease, including mild-tomoderate emphysema, lung inflammation, and airway remodeling, also showed higher IFN response to RV than normal, and this was associated with heightened lung inflammation (5). We also showed that RV interaction with TLR2 is required for limiting replication-dependent antiviral type I and type III IFN expression in normal airway epithelial cells (6).…”

mentioning

confidence: 60%

Rhinovirus-Induced SIRT-1 via TLR2 Regulates Subsequent Type I and Type III IFN Responses in Airway Epithelial Cells

Xander

Vari

Eskandar

et al. 2019

The Journal of Immunology

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IFN responses to viral infection are necessary to establish intrinsic antiviral state, but if unchecked can lead to heightened inflammation. Recently, we showed that TLR2 activation contributes to limitation of rhinovirus (RV)–induced IFN response in the airway epithelial cells. We also demonstrated that compared with normal airway epithelial cells, those from patients with chronic obstructive pulmonary disease (COPD) show higher IFN responses to RV, but the underlying mechanisms are not known. Initially, RV-induced IFN responses depend on dsRNA receptor activation and then are amplified via IFN-stimulated activation of JAK/STAT signaling. In this study, we show that in normal cells, TLR2 limits RV-induced IFN responses by attenuating STAT1 and STAT2 phosphorylation and this was associated with TLR2-dependent SIRT-1 expression. Further, inhibition of SIRT-1 enhanced RV-induced IFN responses, and this was accompanied by increased STAT1/STAT2 phosphorylation, indicating that TLR2 may limit RV-induced IFN responses via SIRT-1. COPD airway epithelial cells showed attenuated IL-8 responses to TLR2 agonist despite expressing TLR2 similar to normal, indicating dysregulation in TLR2 signaling pathway. Unlike normal, COPD cells failed to show RV-induced TLR2-dependent SIRT-1 expression. Pretreatment with quercetin, which increases SIRT-1 expression, normalized RV-induced IFN levels in COPD airway epithelial cells. Inhibition of SIRT-1 in quercetin-pretreated COPD cells abolished the normalizing effects of quercetin on RV-induced IFN expression in these cells, confirming that quercetin exerts its effect via SIRT-1. In summary, we show that TLR2 is required for limiting RV-induced IFNs, and this pathway is dysregulated in COPD airway epithelial cells, leading to exaggerated IFN production.

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confidence: 60%

Rhinovirus-Induced SIRT-1 via TLR2 Regulates Subsequent Type I and Type III IFN Responses in Airway Epithelial Cells

Xander

Vari

Eskandar

et al. 2019

The Journal of Immunology

Self Cite

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“…The results of a recent study showed that quercetin supplementation reduced all pathological changes in mice with rhinovirus-induced chronic obstructive pulmonary disease (COPD) and might prevent pulmonary disease progression in COPD. [16] Another experiment confirmed that quercetin could enhance ligand-induced senescent idiopathic pulmonary fibrosis fibroblast apoptosis and reduce lung fibrosis in vivo. [17] Luteolin has been proved to improve experimental pulmonary fibrosis in vivo and in vitro [18] and attenuate acute lung injury in experimental mouse models [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 93%

In silico screening of potential anti–COVID-19 bioactive natural constituents from food sources by molecular docking

Gao

Liang³

et al. 2021

Nutrition

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Highlights Screen potential anti-COVID-19 bioactive natural ingredients from food sources through high-throughput molecular docking. Quercetin, Luteolin and Isorhamnetin as antiviral active phytocompounds Red wine, Chinese hawthorn and blackberry are rich dietary sources of polyphenols with reported health benefits, and they are recommended as preventive supplements

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“…IFNα/β deficiency has been demonstrated in bronchial biopsies of asthmatic patients with rhinovirus-induced exacerbations and smokinginduced COPD (103). Farazuddin et al have demonstrated that quercetin, a potent antioxidant and anti-inflammatory agent with antiviral properties, effectively mitigates rhinovirus-induced COPD exacerbation in a mouse model (104). Elevated ICAM-1 expression on the surface of airway epithelium has been directly linked to the mechanism of increased susceptibility of HRVinduced acute exacerbation.…”

Section: Cytoplasmic-sensing Pathwaysmentioning

confidence: 99%

Mechanisms of Virus-Induced Airway Immunity Dysfunction in the Pathogenesis of COPD Disease, Progression, and Exacerbation

et al. 2020

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Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation. COPD is characterized by acute pulmonary exacerbations and associated accelerated lung function decline, hospitalization, readmission and an increased risk of mortality, leading to huge social-economic burdens. Recent evidence suggests ∼50% of COPD acute exacerbations are connected with a range of respiratory viral infections. Nevertheless, respiratory viral infections have been linked to the severity and frequency of exacerbations and virus-induced secondary bacterial infections often result in a synergistic decline of lung function and longer hospitalization. Here, we review current advances in understanding the cellular and molecular mechanisms underlying the pathogenesis of COPD and the increased susceptibility to virus-induced exacerbations and associated immune dysfunction in patients with COPD. The multiple immune regulators and inflammatory signaling pathways known to be involved in host-virus responses are discussed. As respiratory viruses primarily target airway epithelial cells, virus-induced inflammatory responses in airway epithelium are of particular focus. Targeting virus-induced inflammatory pathways in airway epithelial cells such as Toll like receptors (TLRs), interferons, inflammasomes, or direct blockade of virus entry and replication may represent attractive future therapeutic targets with improved efficacy. Elucidation of the cellular and molecular mechanisms of virus infections in COPD pathogenesis will undoubtedly facilitate the development of these potential novel therapies that may attenuate the relentless progression of this heterogeneous and complex disease and reduce morbidity and mortality.

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Quercetin prevents rhinovirus-induced progression of lung disease in mice with COPD phenotype

Cited by 61 publications

References 37 publications

Rhinovirus-Induced SIRT-1 via TLR2 Regulates Subsequent Type I and Type III IFN Responses in Airway Epithelial Cells

Rhinovirus-Induced SIRT-1 via TLR2 Regulates Subsequent Type I and Type III IFN Responses in Airway Epithelial Cells

In silico screening of potential anti–COVID-19 bioactive natural constituents from food sources by molecular docking

Mechanisms of Virus-Induced Airway Immunity Dysfunction in the Pathogenesis of COPD Disease, Progression, and Exacerbation

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