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 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.

Paraoxonase-2 deficiency enhancesPseudomonas aeruginosaquorum sensing in murine tracheal epithelia

2007 ◽  
Vol 292 (4) ◽  
pp. L852-L860 ◽  
Author(s):  
David A. Stoltz ◽  
Egon A. Ozer ◽  
Carey J. Ng ◽  
Janet M. Yu ◽  
Srinivasa T. Reddy ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Quorum Sensing ◽  
Airway Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
Tracheal Epithelial Cells ◽  
Human Airway ◽  
Tracheal Epithelial

Pseudomonas aeruginosa is an important cause of nosocomial infections and is frequently present in the airways of cystic fibrosis patients. Quorum sensing mediates P. aeruginosa's virulence and biofilm formation through density-dependent interbacterial signaling with autoinducers. N-3-oxododecanoyl homoserine lactone (3OC12-HSL) is the major autoinducer in P. aeruginosa. We have previously shown that human airway epithelia and paraoxonases (PONs) degrade 3OC12-HSL. This study investigated the role of PON1, PON2, and PON3 in airway epithelial cell inactivation of 3OC12-HSL. All three PONs were present in murine tracheal epithelial cells, with PON2 and PON3 expressed at the highest levels. Lysates of tracheal epithelial cells from PON2, but not PON1 or PON3, knockout mice had impaired 3OC12-HSL inactivation compared with wild-type mice. In contrast, PON1-, PON2-, or PON3-targeted deletions did not affect 3OC12-HSL degradation by intact epithelia. Overexpression of PON2 enhanced 3OC12-HSL degradation by human airway epithelial cell lysates but not by intact epithelia. Finally, using a quorum-sensing reporter strain of P. aeruginosa, we found that quorum sensing was enhanced in PON2-deficient airway epithelia. In summary, these results show that loss of PON2 impairs 3OC12-HSL degradation by airway epithelial cells and suggests that diffusion of 3OC12-HSL into the airway cells can be the rate-limiting step for degradation of the molecule.

Hog barn dust extract augments lymphocyte adhesion to human airway epithelial cells

2004 ◽  
Vol 96 (5) ◽  
pp. 1738-1744 ◽  
Author(s):  
T. Mathisen ◽  
S. G. Von Essen ◽  
T. A. Wyatt ◽  
D. J. Romberger
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Function ◽  
Airway Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Intercellular Adhesion Molecule ◽  
Airway Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Lymphocyte Adhesion ◽  
Dust Extract

The dust of hog confinement facilities induces airway inflammation. Mechanisms by which this dust modulates inflammation are not completely defined, although it is clear that exposure to dust can modulate both epithelial cell and inflammatory cell function. In this work, we demonstrate that airway epithelial cell (BEAS-2B) treatment with hog barn dust extract (HDE) results in augmentation of peripheral blood lymphocyte adhesion to epithelial cell cultures in vitro. The augmentation of lymphocyte adhesion to epithelial cells is dependent on the concentration of HDE and time of HDE exposure, with twofold increases observed by 3 h and maintained at 24 h. Similar results are seen with primary human bronchial epithelial cells in culture. Lymphocyte adhesion to epithelial cells is inhibited in a concentration-dependent fashion by the treatment of epithelial cells with antibody to intercellular adhesion molecule-1 (ICAM-1). In addition, HDE exposure of epithelial cells results in an approximate twofold increase in ICAM-1 expression as determined by flow cytometry analysis. Pretreatment of epithelial cells with a protein kinase C-α (PKC-α) inhibitor, Gö-6976, also inhibited subsequent lymphocyte adhesion to HDE-exposed epithelial cells. These data suggest that airway epithelial cell HDE exposure enhances subsequent lymphocyte adhesion to epithelial cells that is mediated in part by HDE modulation of ICAM-1 expression and PKC-α.

scholarly journals Cooperative effects of rhinovirus and TNF-α on airway epithelial cell chemokine expression

2007 ◽  
Vol 293 (4) ◽  
pp. L1021-L1028 ◽  
Author(s):  
Dawn C. Newcomb ◽  
Umadevi S. Sajjan ◽  
Deepti R. Nagarkar ◽  
Adam M. Goldsmith ◽  
J. Kelley Bentley ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Epithelial Cell ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Obstructive Pulmonary Disease ◽  
Cooperative Effects ◽  
Tracheal Epithelial Cells ◽  
Chemokine Expression ◽  
Tnf Α

Rhinovirus (RV) infections trigger exacerbations of airways disease, but underlying mechanisms remain unknown. We hypothesized that RV and cytokines present in inflamed airways combine to induce augmented airway epithelial cell chemokine expression, promoting further inflammation. To test this hypothesis in a cellular system, we examined the combined effects of RV39 and TNF-α, a cytokine increased in asthma and chronic obstructive pulmonary disease, on airway epithelial cell proinflammatory gene expression. Costimulation of 16HBE14o- human bronchial epithelial cells and primary mucociliary-differentiated tracheal epithelial cells with RV and TNF-α induced synergistic increases in IL-8 and epithelial neutrophil attractant-78 production. Similar synergism was observed for IL-8 promoter activity, demonstrating that the effect is transcriptionally mediated. Whereas increases in ICAM-1 expression and viral load were noted 16–24 h after costimulation, cooperative effects between RV39 and TNF-α were evident 4 h after stimulation and maintained despite incubation with blocking antibody to ICAM-1 given 2 h postinfection or UV irradiation of virus, implying that effects were not solely due to changes in ICAM-1 expression. Furthermore, RV39 infection induced phosphorylation of ERK and transactivation of the IL-8 promoter AP-1 site, which functions as a basal level enhancer, leading to enhanced TNF-α responses. We conclude that RV infection and TNF-α stimulation induce cooperative increases in epithelial cell chemokine expression, providing a cellular mechanism for RV-induced exacerbations of airways disease.

scholarly journals Influenza Virus Receptor Specificity and Cell Tropism in Mouse and Human Airway Epithelial Cells

2006 ◽  
Vol 80 (15) ◽  
pp. 7469-7480 ◽  
Author(s):  
Aida Ibricevic ◽  
Andrew Pekosz ◽  
Michael J. Walter ◽  
Celeste Newby ◽  
John T. Battaile ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Influenza Viruses ◽  
Mouse Lung ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

ABSTRACT Recent human infections caused by the highly pathogenic avian influenza virus H5N1 strains emphasize an urgent need for assessment of factors that allow viral transmission, replication, and intra-airway spread. Important determinants for virus infection are epithelial cell receptors identified as glycans terminated by an α2,3-linked sialic acid (SA) that preferentially bind avian strains and glycans terminated by an α2,6-linked SA that bind human strains. The mouse is often used as a model for study of influenza viruses, including recent avian strains; however, the selectivity for infection of specific respiratory cell populations is not well described, and any relationship between receptors in the mouse and human lungs is incompletely understood. Here, using in vitro human and mouse airway epithelial cell models and in vivo mouse infection, we found that the α2,3-linked SA receptor was expressed in ciliated airway and type II alveolar epithelial cells and was targeted for cell-specific infection in both species. The α2,6-linked SA receptor was not expressed in the mouse, a factor that may contribute to the inability of some human strains to efficiently infect the mouse lung. In human airway epithelial cells, α2,6-linked SA was expressed and functional in both ciliated and goblet cells, providing expanded cellular tropism. Differences in receptor and cell-specific expression in these species suggest that differentiated human airway epithelial cell cultures may be superior for evaluation of some human strains, while the mouse can provide a model for studying avian strains that preferentially bind only the α2,3-linked SA receptor.

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 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.

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