scholarly journals Oxidized phosphatidylcholines induce multiple functional defects in airway epithelial cells

2019 ◽  
Author(s):  
Christopher D Pascoe ◽  
Neilloy Roy ◽  
Emily Turner-Brannen ◽  
Alexander Schultz ◽  
Jignesh Vaghasiya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Barrier Function ◽  
Allergen Challenge ◽  
Airway Epithelial Cells ◽  
Bioactive Molecules ◽  
Partial Recovery ◽  
Airway Epithelial

ABSTRACTOxidative stress is a hallmark of numerous airway diseases, contributing to extensive cell and tissue damage. Cell membranes and the airway mucosal lining are rich in phospholipids that are particularly susceptible to oxidative attack, producing bioactive molecules including oxidized phosphatidylcholines (OxPC). With the recent discovery of elevated OxPC in asthmatic patients after allergen challenge, we hypothesized that OxPC directly contribute to disease by inducing airway epithelial cell dysfunction.We found that OxPC induced dose-dependent cell stress and loss of viability in BEAS-2B and Calu-3 cell lines and primary human epithelial cells. These responses corresponded with significant epithelial barrier dysfunction, which was further compounded when combining OxPC with an epithelial wound. OxPC inhibited DNA synthesis and migration required to re-establish barrier function, but cells recovered if OxPC were washed off soon after treatment. OxPC induced generation of reactive oxygen species, lipid peroxidation and mitochondrial dysfunction, raising the possibility that OxPC cause pathological lipid metabolism in a self-propagating cycle. The oxidative stress induced by OxPC could not be abrogated by putative OxPC receptor blockers, but partial recovery of barrier function, proliferation and lipid peroxidation could be achieved with the antioxidant n-acetyl cysteine.In summary, we have identified OxPC as a group of bioactive molecules that significantly impair multiple facets of epithelial cell function, consistent with pathological features of asthma. Further characterisation of the mechanisms by which OxPC affect epithelial cells could yield new insights into how oxidative stress contributes to the pathogenesis of airway disease.

Oxidized Phosphatidylcholines Induce Multiple Functional Defects in Airway Epithelial Cells

2021 ◽  
Author(s):  
Christopher D Pascoe ◽  
Neilloy Roy ◽  
Emily Turner-Brannen ◽  
Alexander Schultz ◽  
Jignesh Vaghasiya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Barrier Function ◽  
Allergen Challenge ◽  
Airway Epithelial Cells ◽  
Bioactive Molecules ◽  
Partial Recovery ◽  
Airway Epithelial

Oxidative stress is a hallmark of numerous airway diseases, contributing to extensive cell and tissue damage. Cell membranes and the airway mucosal lining are rich in phospholipids that are particularly susceptible to oxidative attack, producing bioactive molecules including oxidized phosphatidylcholines (OxPC). With the recent discovery of elevated OxPC in asthmatic patients after allergen challenge, we hypothesized that OxPC directly contribute to disease by inducing airway epithelial cell dysfunction. We found that OxPC induced concentration-dependent cell stress and loss of viability in BEAS-2B and Calu-3 cell lines and primary human epithelial cells. These responses corresponded with significant epithelial barrier dysfunction, which was further compounded when combining OxPC with an epithelial wound. OxPC inhibited DNA synthesis and migration required to re-establish barrier function, but cells recovered if OxPC were washed off soon after treatment. OxPC induced generation of reactive oxygen species, lipid peroxidation and mitochondrial dysfunction, raising the possibility that OxPC cause pathological lipid metabolism in a self-propagating cycle. The oxidative stress induced by OxPC could not be abrogated by putative OxPC receptor blockers, but partial recovery of barrier function, proliferation and lipid peroxidation could be achieved with the antioxidant n-acetyl cysteine. In summary, we have identified OxPC as a group of bioactive molecules that significantly impair multiple facets of epithelial cell function, consistent with pathological features of asthma. Further characterisation of the mechanisms by which OxPC affect epithelial cells could yield new insights into how oxidative stress contributes to the pathogenesis of airway disease.

scholarly journals Effective-Component Compatibility of Bufei Yishen Formula Ⅲ Ameliorated COPD By Improving Airway Epithelial Cell Senescence Via Promoting Mitophagy By Nrf2/PINK1 Pathway

2022 ◽  
Author(s):  
Min-yan Li ◽  
Yan-qin Qin ◽  
Jian-sheng Li ◽  
Peng Zhao ◽  
Yan-ge Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Cell Senescence ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Positive Effects ◽  
Effective Component

Abstract Background: Effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYF Ⅲ) shows positive effects on stable chronic obstructive pulmonary disease (COPD).Purpose: To investigate the mechanisms of ECC-BYF Ⅲ on COPD rats from the aspect of airway epithelial cell senescence.Methods: COPD model rats were treated with ECC-BYF Ⅲ for 8 weeks and the efficacy was evaluated. Cigarette smoke extract (CSE) induced senescence model of airway epithelial cells were treated with ECC-BYF Ⅲ, the related enzymes and proteins involved in oxidative stress and mitophagy were detected.Results: ECC-BYF Ⅲ markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9, increase of the level of total superoxide dismutase (T-SOD), and decease of p21 level in airway. Furthermore, ECC-BYF Ⅲ suppressed p16, p21 expressions and senescence-associated β-galactosidase (SA-β-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF Ⅲ upregulated the mitophagy-related proteins, including co-localization of TOM20 and LC3B, PINK1, PARK2, and improved mitochondrial function with upregulating mitochondrial mitofusin (Mfn)2 and reducing dynamin-related protein 1 (Drp1) expression. ECC-BYF Ⅲ enhanced the activities of T-SOD and GSH-PX by up-regulating Nrf2, thus inhibiting oxidative stress. After intervention with Nrf2 inhibitor, the regulation effects of ECC-BYF Ⅲ on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed.Conclusions: ECC-BYF Ⅲ exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through activation of Nrf2 signaling.

scholarly journals Ozone effect on inflammatory and proteomic profile of human macrophages and airway epithelial cells

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
L Falcone ◽  
E Aruffo ◽  
P Di Carlo ◽  
P Del Boccio ◽  
M C Cufaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Air Pollution ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Urban Areas ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Proteomics Analysis ◽  
Human Macrophages ◽  
Tnf Α

Abstract Background Reactive oxygen species (ROS) and oxidative stress in the respiratory system are involved in lung inflammation and tumorigenesis. Ozone (O3) is one of the main components of air pollution in urban areas able to act as strong pro-oxidant agent, however its effects on human health is still poorly investigated. In this study the effect of O3 has been evaluated in THP-1 monocytes differentiated into macrophages with PMA and in HBEpC (primary human bronchial epithelial) cells, two model systems for in vitro studies and translational research. Methods Cell viability, ROS and pro-inflammatory cytokines like interleukin-8(IL-8) and tumor necrosis factor(TNF-α) have been tested in the above-mentioned cell lines not exposed to any kind of pollution (basal condition-b.c.) or exposed to O3 at a concentration of 120 ppb. In HBEpC a labelfree shotgun proteomics analysis has been also performed in the same conditions. Results Ozone significantly increased the production of IL-8 and TNF-α in THP-1 whereas no changes were shown in HBEpC. In both cell lines lipopolysaccharide(LPS) caused an increase of IL-8 and TNF-α production in b.c. and O3 treatment potentiated this effect. Ozone exposure increased ROS formation in a time dependent manner in both cell lines and in THP-1 cells a decrease in catalase activity was also shown. Finally, according to these data, functional proteomics analysis revealed that in HBEpC exposure to O3 many differential proteins are related to oxidative stress and inflammation. Conclusions Our results indicate that O3, at levels that can be reached in urban areas, causes an increase of pro-inflammatory agents either per se or potentiating the effect of immune response stimulators in cell models of human macrophages and human airway epithelial cells. Interestingly, the proteomic analysis showed that besides the dysregulated proteins, O3 induced the expression of AKR1D1 and AKR1B10, proteins recognized to play a significant role in cancer development. Key messages This study adds new pieces of information on the association between O3 exposure and detrimental effects on respiratory system. This study suggests the need for further research on the mechanisms involved and for a continued monitoring/re-evaluation of air pollution standards aimed at safeguarding human health.

scholarly journals Infection of bovine well-differentiated airway epithelial cells by Pasteurella multocida: actions and counteractions in the bacteria–host interactions

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Ang Su ◽  
Jie Tong ◽  
Yuguang Fu ◽  
Sandy Müller ◽  
Yenehiwot Berhanu Weldearegay ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Layer ◽  
Airway Epithelial Cells ◽  
Infection Model ◽  
Target Cells ◽  
Respiratory Disorder ◽  
Airway Epithelial ◽  
Epithelial Cell Layer ◽  
Well Differentiated

AbstractPasteurella (P.) multocida is a zoonotic pathogen, which is able to cause respiratory disorder in different hosts. In cattle, P. multocida is an important microorganism involved in the bovine respiratory disease complex (BRDC) with a huge economic impact. We applied air–liquid interface (ALI) cultures of well-differentiated bovine airway epithelial cells to analyze the interaction of P. multocida with its host target cells. The bacterial pathogen grew readily on the ALI cultures. Infection resulted in a substantial loss of ciliated cells. Nevertheless, the epithelial cell layer maintained its barrier function as indicated by the transepithelial electrical resistance and the inability of dextran to get from the apical to the basolateral compartment via the paracellular route. Analysis by confocal immunofluorescence microscopy confirmed the intactness of the epithelial cell layer though it was not as thick as the uninfected control cells. Finally, we chose the bacterial neuraminidase to show that our infection model is a sustainable tool to analyze virulence factors of P. multocida. Furthermore, we provide an explanation, why this microorganism usually is a commensal and becomes pathogenic only in combination with other factors such as co-infecting microorganisms.

scholarly journals FOXO3a regulates rhinovirus-induced innate immune responses in airway epithelial cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joao Gimenes-Junior ◽  
Nicole Owuar ◽  
Hymavathi Reddy Vari ◽  
Wuyan Li ◽  
Nathaniel Xander ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Lung Inflammation ◽  
Inflammatory Cytokine ◽  
Airway Epithelial Cell ◽  
Critical Role ◽  
Airway Epithelial Cells ◽  
Type I ◽  
Airway Epithelial ◽  
Antiviral Responses

AbstractForkhead transcription factor class O (FOXO)3a, which plays a critical role in a wide variety of cellular processes, was also found to regulate cell-type-specific antiviral responses. Airway epithelial cells express FOXO3a and play an important role in clearing rhinovirus (RV) by mounting antiviral type I and type III interferon (IFN) responses. To elucidate the role of FOXO3a in regulating antiviral responses, we generated airway epithelial cell-specific Foxo3a knockout (Scga1b1-Foxo3a−/−) mice and a stable FOXO3a knockout human airway epithelial cell line. Compared to wild-type, Scga1b1-Foxo3a−/− mice show reduced IFN-α, IFN-β, IFN-λ2/3 in response to challenge with RV or double-stranded (ds)RNA mimic, Poly Inosinic-polycytidylic acid (Poly I:C) indicating defective dsRNA receptor signaling. RV-infected Scga1b1-Foxo3a−/− mice also show viral persistence, enhanced lung inflammation and elevated pro-inflammatory cytokine levels. FOXO3a K/O airway epithelial cells show attenuated IFN responses to RV infection and this was associated with conformational change in mitochondrial antiviral signaling protein (MAVS) but not with a reduction in the expression of dsRNA receptors under unstimulated conditions. Pretreatment with MitoTEMPO, a mitochondrial-specific antioxidant corrects MAVS conformation and restores antiviral IFN responses to subsequent RV infection in FOXO3a K/O cells. Inhibition of oxidative stress also reduces pro-inflammatory cytokine responses to RV in FOXO3a K/O cells. Together, our results indicate that FOXO3a plays a critical role in regulating antiviral responses as well as limiting pro-inflammatory cytokine expression. Based on these results, we conclude that FOXO3a contributes to optimal viral clearance and prevents excessive lung inflammation following RV infection.

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