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Article: The DmsABC S-oxide reductase is an essential component of a novel, hypochlorite-inducible system of extracellular stress defense in

Nasreen, Marufa / Ellis, Daniel / Hosmer, Jennifer / Essilfie, Ama-Tawiah / Fantino, Emmanuelle / Sly, Peter / McEwan, Alastair G / Kappler, Ulrike

Frontiers in microbiology

2024 Volume 15, Page(s) 1359513

Abstract: Defenses against oxidative damage to cell components are essential for survival of bacterial pathogens during infection, and here we have uncovered that the DmsABC S-/N-oxide reductase is essential for virulence and in-host survival of the human-adapted ... ...

Abstract	Defenses against oxidative damage to cell components are essential for survival of bacterial pathogens during infection, and here we have uncovered that the DmsABC S-/N-oxide reductase is essential for virulence and in-host survival of the human-adapted pathogen,
Language	English
Publishing date	2024-04-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2024.1359513
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Article ; Online: CFTR is required for zinc-mediated antibacterial defense in human macrophages.

Das Gupta, Kaustav / Curson, James E B / Tarique, Abdullah A / Kapetanovic, Ronan / Schembri, Mark A / Fantino, Emmanuelle / Sly, Peter D / Sweet, Matthew J

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 8, Page(s) e2315190121

Abstract: Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion transporter required for epithelial homeostasis in the lung and other organs, ... ...

Abstract	Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion transporter required for epithelial homeostasis in the lung and other organs, with
MeSH term(s)	Humans ; Anti-Bacterial Agents/therapeutic use ; Cystic Fibrosis/microbiology ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Macrophages/metabolism ; Macrophages/microbiology ; Zinc/metabolism
Chemical Substances	Anti-Bacterial Agents ; CFTR protein, human ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2315190121
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Article ; Online: Resveratrol and Astaxanthin Protect Primary Human Nasal Epithelial Cells Cultured at an Air-liquid Interface from an Acute Oxidant Exposure.

Yamamoto, Ayaho / Sly, Peter D / Begum, Nelufa / Yeo, Abrey J / Fantino, Emmanuelle

Journal of cellular signaling

2023 Volume 3, Issue 4, Page(s) 207–217

Abstract: Oxidative stress (OS) in the airway epithelium is associated with cell damage, inflammation, and mitochondrial dysfunction that may initiate or worsen respiratory disease. However, it is unclear whether exogenous antioxidants can provide protection to ... ...

Abstract	Oxidative stress (OS) in the airway epithelium is associated with cell damage, inflammation, and mitochondrial dysfunction that may initiate or worsen respiratory disease. However, it is unclear whether exogenous antioxidants can provide protection to the airway epithelium from OS. Resveratrol and astaxanthin are nutritional compounds that have shown diverse benefits including protection against OS and inflammation in various situations. The aim of this study was to examine the utility of pre-treatment with resveratrol and astaxanthin to prevent the negative effects of oxidant exposure and restore redox homeostasis in a well-differentiated epithelium grown from primary human nasal epithelial cells (NECs) at the air-liquid interface. Fully differentiated NECs were pretreated with the antioxidants for 24 hours and the cultured epithelia was subsequently exposed to hydrogen peroxide (H
Language	English
Publishing date	2023-01-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	3040876-3
ISSN	2692-0638 ; 2692-0638
ISSN (online)	2692-0638
ISSN	2692-0638
DOI	10.33696/signaling.3.084
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Article ; Online: Redox Homeostasis in Well-differentiated Primary Human Nasal Epithelial Cells.

Yamamoto, Ayaho / Sly, Peter D / Henningham, Anna / Begum, Nelufa / Yeo, Abrey J / Fantino, Emmanuelle

Journal of cellular signaling

2022 Volume 3, Issue 4, Page(s) 193–206

Abstract: Oxidative stress (OS) in the airway epithelium is associated with inflammation, cell damage, and mitochondrial dysfunction that may initiate or worsen respiratory disease. Redox regulation maintains the equilibrium of pro-oxidant/antioxidant reactions ... ...

Abstract	Oxidative stress (OS) in the airway epithelium is associated with inflammation, cell damage, and mitochondrial dysfunction that may initiate or worsen respiratory disease. Redox regulation maintains the equilibrium of pro-oxidant/antioxidant reactions but can be disturbed by environmental exposures. The mechanism(s) underlying the induction and impact of OS on airway epithelium and how these influences on respiratory disease is poorly understood. The aim of this study was to develop a stress response model in primary human nasal epithelial cells (NECs) grown at the air-liquid interface (ALI) into a well-differentiated epithelium and to use this model to investigate the mechanisms underlying OS. Hydrogen peroxide (H
Language	English
Publishing date	2022-12-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	3040876-3
ISSN	2692-0638 ; 2692-0638
ISSN (online)	2692-0638
ISSN	2692-0638
DOI	10.33696/signaling.3.083
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Article ; Online: COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV.

Collinson, Natasha / Snape, Natale / Beagley, Kenneth / Fantino, Emmanuelle / Spann, Kirsten

Viruses

2021 Volume 13, Issue 5

Abstract: IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the ... ...

Abstract	IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV. BECs from five COPD and five healthy donors were used to establish both submerged monolayer and well-differentiated (WD) cultures. Two isolates of both RSV and hMPV were used to infect cells. COPD was not associated with elevated susceptibility to infection and there was no evidence of an intrinsic defect in IFN production in either cell model to either virus. Conversely, COPD was associated with significantly elevated IFN-β production in response to both viruses in both cell models. Only in WD-BECs infected with RSV was elevated IFN-β associated with reduced viral shedding. The role of elevated epithelial cell IFN-β production in the pathogenesis of COPD is not clear and warrants further investigation. Viruses vary in the responses that they induce in BECs, and so conclusions regarding antiviral responses associated with disease cannot be made based on single viral infections.
MeSH term(s)	Aged ; Cells, Cultured ; Disease Susceptibility ; Epithelial Cells/virology ; Female ; Humans ; Interferon-beta/biosynthesis ; Male ; Metapneumovirus ; Middle Aged ; Paramyxoviridae Infections/complications ; Paramyxoviridae Infections/virology ; Pulmonary Disease, Chronic Obstructive/etiology ; Pulmonary Disease, Chronic Obstructive/metabolism ; Pulmonary Disease, Chronic Obstructive/pathology ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/pathology ; Respiratory Mucosa/virology ; Respiratory Syncytial Virus Infections/complications ; Respiratory Syncytial Virus Infections/virology ; Respiratory Syncytial Viruses ; Virus Shedding
Chemical Substances	Interferon-beta (77238-31-4)
Language	English
Publishing date	2021-05-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13050911
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Article ; Online: Azithromycin Augments Bacterial Uptake and Anti-Inflammatory Macrophage Polarization in Cystic Fibrosis.

Tarique, Abdullah A / Tuladhar, Neeraj / Kelk, Dean / Begum, Nelufa / Lucas, Richard M / Luo, Lin / Stow, Jennifer L / Wainwright, Claire E / Bell, Scott C / Sly, Peter D / Fantino, Emmanuelle

Cells

2024 Volume 13, Issue 2

Abstract: Background: Azithromycin (AZM) is widely being used for treating patients with cystic fibrosis (pwCF) following clinical trials demonstrating improved lung function and fewer incidents of pulmonary exacerba-tions. While the precise mechanisms remain ... ...

Abstract	Background: Azithromycin (AZM) is widely being used for treating patients with cystic fibrosis (pwCF) following clinical trials demonstrating improved lung function and fewer incidents of pulmonary exacerba-tions. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs), were differentiated into monocyte-derived macrophages (MDMs) and subsequently infected with Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve an improved uptake of both Gram-positive and Gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.
MeSH term(s)	Humans ; Azithromycin/pharmacology ; Gram-Negative Bacteria ; Anti-Bacterial Agents/pharmacology ; Cystic Fibrosis/drug therapy ; Escherichia coli ; Staphylococcus aureus ; Gram-Positive Bacteria ; Macrophages ; Anti-Inflammatory Agents/pharmacology
Chemical Substances	Azithromycin (83905-01-5) ; Anti-Bacterial Agents ; Anti-Inflammatory Agents
Language	English
Publishing date	2024-01-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13020166
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Article ; Online: Neutrophil respiratory burst activity is not exaggerated in cystic fibrosis.

Kelk, Dean / Logan, Jayden / Andersen, Isabella / Gutierrez Cardenas, Diana / Bell, Scott C / Wainwright, Claire E / Sly, Peter D / Fantino, Emmanuelle

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

2022 Volume 21, Issue 4, Page(s) 707–712

Abstract: Background: Exaggerated neutrophil-dominated inflammation underlies progressive cystic fibrosis (CF) lung disease. Older studies reported a defective respiratory burst in CF, but more recent studies suggest neutrophil function is normal.: Methods: We ...

Abstract	Background: Exaggerated neutrophil-dominated inflammation underlies progressive cystic fibrosis (CF) lung disease. Older studies reported a defective respiratory burst in CF, but more recent studies suggest neutrophil function is normal. Methods: We measured the amount and rate of reactive oxygen species (ROS) during PMA-stimulated respiratory burst activity in children [70 CF, 13 disease controls, 19 health controls] and adults [31 CF, 14 health controls] in neutrophils harvested from peripheral blood. Blood was collected from participants with CF when clinically stable (60 children, 9 adults) and on hospital admission (38 children, 24 adults) and discharge (18 children, 21 adults) for acute pulmonary exacerbations. Results: When clinically stable, children with CF had lower ROS production [median 318,633, 25% 136,810 - 75% 569,523 RLU] than disease controls [median 599,459, 25% 425,566 - 75% 730,527 RLU] and healthy controls [median 534,073, 25% 334,057 - 75% 738,593 RLU] (p = 0.008). The rate of ROS production was also lower (p = 0.029). In neither children nor adults with CF did ROS production increase on hospital admission for acute pulmonary exacerbation, nor fall prior to discharge. There were no associations between ROS production and high-sensitivity C-reactive protein (indicating systemic inflammation) in either children or adults with CF. Conclusions: Our data do not support a role for exaggerated respiratory burst activity contributing to the exaggerated neutrophil-dominated inflammation seen with CF lung disease.
MeSH term(s)	Adult ; Child ; Cystic Fibrosis ; Humans ; Inflammation/metabolism ; Neutrophils/metabolism ; Reactive Oxygen Species/metabolism ; Respiratory Burst
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2022-01-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2084724-5
ISSN	1873-5010 ; 1569-1993
ISSN (online)	1873-5010
ISSN	1569-1993
DOI	10.1016/j.jcf.2021.12.015
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Zs.A 6028: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 459: Show issues

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Article ; Online: Characterizing well-differentiated culture of primary human nasal epithelial cells for use in wound healing assays.

Schagen, Johanna / Sly, Peter D / Fantino, Emmanuelle

Laboratory investigation; a journal of technical methods and pathology

2018 Volume 98, Issue 11, Page(s) 1478–1486

Abstract: The nasal epithelium is the initial contact between the external environment and the respiratory tract and how it responds to noxious stimuli and repairs epithelial damage is important. Growing airway epithelial cells in culture at air-liquid interface ... ...

Abstract	The nasal epithelium is the initial contact between the external environment and the respiratory tract and how it responds to noxious stimuli and repairs epithelial damage is important. Growing airway epithelial cells in culture at air-liquid interface allows for a physiologically relevant model of the human upper airways. The aim of the present study was to characterize human primary nasal epithelial cells grown at the air-liquid interface and establish a model for use in wound healing assays. This study determined the time required for full differentiation of nasal epithelial cells in an air-liquid interface culture to be at least 7 weeks using the standardized B-ALI media. Also, a model was established that studied the response to wounding and the effect of EGFR inhibition on this process. Nasal epithelial cultures from healthy subjects were differentiated at air-liquid interface and manually wounded. Wounds were monitored over time to complete closure using a time lapse imaging microscope with cultures identified to have a rate of wound healing above 2.5%/h independent of initial wound size. EGFR inhibition caused the rate of wound healing to drop a significant 4.6%/h with there being no closure of the wound after 48 h. The robust model established in this study will be essential for studying factors influencing wound healing, including host disease status and environmental exposures in the future.
MeSH term(s)	Cell Differentiation ; Cytokines/metabolism ; ErbB Receptors/antagonists & inhibitors ; Erlotinib Hydrochloride ; Female ; Humans ; Male ; Nasal Mucosa/cytology ; Primary Cell Culture ; Wound Healing
Chemical Substances	Cytokines ; Erlotinib Hydrochloride (DA87705X9K) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2018-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80178-1
ISSN	1530-0307 ; 0023-6837
ISSN (online)	1530-0307
ISSN	0023-6837
DOI	10.1038/s41374-018-0100-1
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Ud II Zs.164: Show issues

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Article ; Online: Environmentally persistent free radicals enhance SARS-CoV-2 replication in respiratory epithelium.

Yamamoto, Ayaho / Sly, Peter D / Chew, Keng Yih / Khachatryan, Lavrent / Begum, Nelufa / Yeo, Abrey J / Vu, Luan D / Short, Kirsty R / Cormier, Stephania A / Fantino, Emmanuelle

Experimental biology and medicine (Maywood, N.J.)

2023 Volume 248, Issue 3, Page(s) 271–279

Abstract: Epidemiological evidence links lower air quality with increased incidence and severity of COVID-19; however, mechanistic data have yet to be published. We hypothesized air pollution-induced oxidative stress in the nasal epithelium increased viral ... ...

Abstract	Epidemiological evidence links lower air quality with increased incidence and severity of COVID-19; however, mechanistic data have yet to be published. We hypothesized air pollution-induced oxidative stress in the nasal epithelium increased viral replication and inflammation. Nasal epithelial cells (NECs), collected from healthy adults, were grown into a fully differentiated epithelium. NECs were infected with the ancestral strain of SARS-CoV-2. An oxidant combustion by-product found in air pollution, the environmentally persistent free radical (EPFR) DCB230, was used to mimic pollution exposure four hours prior to infection. Some wells were pretreated with antioxidant, astaxanthin, for 24 hours prior to EPFR-DCB230 exposure and/or SARS-CoV-2 infection. Outcomes included viral replication, epithelial integrity, surface receptor expression (
MeSH term(s)	Humans ; SARS-CoV-2/metabolism ; COVID-19/metabolism ; Antioxidants/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Free Radicals/metabolism ; Cytokines/metabolism ; Respiratory Mucosa/metabolism ; Oxidants/metabolism
Chemical Substances	Antioxidants ; Tumor Necrosis Factor-alpha ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; astaxanthine (8XPW32PR7I) ; Free Radicals ; Cytokines ; Oxidants
Language	English
Publishing date	2023-01-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/15353702221142616
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Article: COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV

Collinson, Natasha / Snape, Natale / Beagley, Kenneth / Fantino, Emmanuelle / Spann, Kirsten

Viruses. 2021 May 14, v. 13, no. 5

2021

Abstract	IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV. BECs from five COPD and five healthy donors were used to establish both submerged monolayer and well-differentiated (WD) cultures. Two isolates of both RSV and hMPV were used to infect cells. COPD was not associated with elevated susceptibility to infection and there was no evidence of an intrinsic defect in IFN production in either cell model to either virus. Conversely, COPD was associated with significantly elevated IFN-β production in response to both viruses in both cell models. Only in WD-BECs infected with RSV was elevated IFN-β associated with reduced viral shedding. The role of elevated epithelial cell IFN-β production in the pathogenesis of COPD is not clear and warrants further investigation. Viruses vary in the responses that they induce in BECs, and so conclusions regarding antiviral responses associated with disease cannot be made based on single viral infections.
Keywords	Enterovirus ; epithelial cells ; epithelium ; influenza ; models ; pathogenesis ; viruses
Language	English
Dates of publication	2021-0514
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13050911
Database	NAL-Catalogue (AGRICOLA)

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