scholarly journals Quercetin Prevents LPS-Induced Oxidative Stress and Inflammation by Modulating NOX2/ROS/NF-kB in Lung Epithelial Cells

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6949
Author(s):  
 Ok-Joo Sul ◽  
Seung Won Ra
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
A549 Cells ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Lung Epithelial Cells ◽  
Tnf Α ◽  
Lung Epithelial ◽  
Cytokine Tumor Necrosis Factor ◽  
Inflammatory Processes ◽  
Mrna And Protein Expression

Oxidative stress caused by the production of reactive oxygen species (ROS) plays a major role in inflammatory processes. We hypothesized that modulation of ROS via quercetin may protect against oxidative stress and inflammation. Thus, this study aimed to investigate the effects of quercetin on oxidative stress and inflammation in lung epithelial A549 cells. The lipopolysaccharide (LPS)-induced elevation of intracellular ROS levels was reduced after quercetin treatment, which also almost completely abolished the mRNA and protein expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) induced by LPS stimulation. In addition, quercetin suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and reduced levels of inflammatory cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6, which had increased significantly after LPS exposure. Our data demonstrated that quercetin decreased ROS-induced oxidative stress and inflammation by suppressing NOX2 production.

The effects of PM10 particles and oxidative stress on macrophages and lung epithelial cells: modulating effects of calcium-signaling antagonists

2007 ◽  
Vol 292 (6) ◽  
pp. L1444-L1451 ◽  
Author(s):  
David M. Brown ◽  
Laura Hutchison ◽  
Kenneth Donaldson ◽  
Vicki Stone
Keyword(s):  
Oxidative Stress ◽  
Calcium Antagonist ◽  
Epithelial Cells ◽  
Calcium Signaling ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Tnf Α ◽  
Lung Epithelial

We have previously examined the ability of air pollution particles (PM10) to promote release of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) from human peripheral blood mononuclear cells and demonstrated a role for calcium as a signaling molecule in this process. We have now studied the ability of oxidative stress induced by a synthetic oxidant tert-butyl hydroperoxide (tBHP) to induce TNF-α production via calcium signaling in the mouse macrophage cell line (J774). The oxidant tBHP significantly increased intracellular calcium and the release of TNF-α in J774 cells, an effect that was reduced to control levels by inhibition of calcium signaling with verapamil, BAPTA-AM, and W-7. This study also investigated interactions between PM10-treated macrophages and epithelial cells by using conditioned medium (CM) from PM10-treated mononuclear cells to stimulate the release of the neutrophil chemoattractant chemokine IL-8 from A549 lung epithelial cells. TNF-α protein release was demonstrated in human mononuclear cells after PM10 treatment, an effect that was inhibited by calcium antagonists. Treatment of A549 cells with monocyte/PM10 CM produced increased IL-8 release that was reduced with CM from monocyte/PM10/calcium antagonist treatments. The expression of ICAM-1 was increased after incubation with CM from monocyte/PM10 treatment, and this increase was prevented by treatment with CM from monocyte/PM10/calcium antagonist. These data demonstrate a link between oxidative stress, calcium, and inflammatory mediator production in macrophages and lung epithelial cells.

Dual mechanism forMycobacterium tuberculosiscytotoxicity on lung epithelial cells

2012 ◽  
Vol 58 (7) ◽  
pp. 909-916 ◽  
Author(s):  
Jorge Castro-Garza ◽  
W. Edward Swords ◽  
Russell K. Karls ◽  
Frederick D. Quinn
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Neutralizing Antibodies ◽  
Cytotoxic Effect ◽  
Alveolar Epithelial Cell ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Lung Epithelial

Mycobacterium tuberculosis strains CDC1551 and Erdman were used to assess cytotoxicity in infected A549 human alveolar epithelial cell monolayers. Strain CDC1551 was found to induce qualitatively greater disruption of A549 monolayers than was strain Erdman, although total intracellular and cell-associated bacterial growth rates over the course of the infections were not significantly different. Cell-free culture supernatants from human monocytic cells infected with either of the 2 M. tuberculosis strains produced a cytotoxic effect on A549 cells, correlating with the amount of tumor necrosis factor alpha (TNF-α) released by the infected monocytes. The addition of TNF-α-neutralizing antibodies to the supernatants from infected monocyte cultures did prevent the induction of a cytotoxic effect on A549 cells overlaid with this mixture but did not prevent the death of epithelial cells when added prior to infection with M. tuberculosis bacilli. Thus, these data agree with previous observations that lung epithelial cells infected with M. tuberculosis bacilli are rapidly killed in vitro. In addition, the data indicate that some of the observed epithelial cell killing may be collateral damage; the result of TNF-α released from M. tuberculosis-infected monocytes.

scholarly journals The antioxidant resveratrol down-regulates inflammation in an in-vitro model of Pseudomonas aeruginosa infection of lung epithelial cells

2013 ◽  
Vol 91 (3) ◽  
pp. 248-255 ◽  
Author(s):  
Ashley M. Cerqueira ◽  
Neelam Khaper ◽  
Simon J. Lees ◽  
Marina Ulanova
Keyword(s):  
Oxidative Stress ◽  
Pseudomonas Aeruginosa ◽  
Inflammatory Response ◽  
A549 Cells ◽  
Surface Expression ◽  
Lung Epithelial Cells ◽  
Cell Surface Expression ◽  
Intercellular Adhesion Molecule ◽  
Ros Generation ◽  
Lung Epithelial

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that can cause severe pulmonary infection in immunocompromized individuals. During the infectious process, P. aeruginosa provokes a potent inflammatory response and induces the release of reactive oxygen species (ROS). Cells undergo oxidative stress when cellular antioxidants are unable to effectively scavenge and detoxify ROS, resulting in lung damage. Resveratrol (3,5,4′-trihydroxystilbene) is a natural polyphenolic compound with recognized antioxidant effects. We hypothesized that owing to its antioxidant activities, resveratrol can attenuate an inflammatory response in P. aeruginosa-infected cells. Lung epithelial A549 cells were pre-treated with 100 μmol/L of resveratrol for 5 h, followed by infection with P. aeruginosa. Intracellular ROS generation was used as an indicator of P. aeruginosa-induced oxidative stress, and cell surface expression of Fas receptor and activation of caspases-3 and -7 as indicators of apoptosis. We also measured the surface expression of intercellular adhesion molecule (ICAM)-1 and enzymes related to inflammation and redox signaling. Resveratrol significantly reduced ROS generation, ICAM-1, and human beta-defensin-2 expression, as well as the markers of apoptosis in A549 cells infected with P. aeruginosa, and up-regulated glutathione peroxidase, suggesting its potential therapeutic role in protecting the lungs against the deleterious effects of P. aeruginosa infection.

Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells

2008 ◽  
Vol 294 (3) ◽  
pp. L478-L488 ◽  
Author(s):  
Aruna Kode ◽  
Saravanan Rajendrasozhan ◽  
Samuel Caito ◽  
Se-Ran Yang ◽  
Ian L. Megson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Posttranslational Modifications ◽  
Nuclear Translocation ◽  
Airway Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Oxygen Species ◽  
Airway Epithelial ◽  
Alveolar Epithelial ◽  
Lung Epithelial

Nuclear erythroid-related factor 2 (Nrf2), a redox-sensitive transcription factor, is involved in transcriptional regulation of many antioxidant genes, including glutamate-cysteine ligase (GCL). Cigarette smoke (CS) is known to cause oxidative stress and deplete glutathione (GSH) levels in alveolar epithelial cells. We hypothesized that resveratrol, a polyphenolic phytoalexin, has antioxidant signaling properties by inducing GSH biosynthesis via the activation of Nrf2 and protects lung epithelial cells against CS-mediated oxidative stress. Treatment of human primary small airway epithelial and human alveolar epithelial (A549) cells with CS extract (CSE) dose dependently decreased GSH levels and GCL activity, effects that were associated with enhanced production of reactive oxygen species. Resveratrol restored CSE-depleted GSH levels by upregulation of GCL via activation of Nrf2 and also quenched CSE-induced release of reactive oxygen species. Interestingly, CSE failed to induce nuclear translocation of Nrf2 in A549 and small airway epithelial cells. On the contrary, Nrf2 was localized in the cytosol of alveolar and airway epithelial cells due to CSE-mediated posttranslational modifications such as aldehyde/carbonyl adduct formation and nitration. On the other hand, resveratrol attenuated CSE-mediated Nrf2 modifications, thereby inducing its nuclear translocation associated with GCL gene transcription, as demonstrated by GCL-promoter reporter and Nrf2 small interfering RNA approaches. Thus resveratrol attenuates CSE-mediated GSH depletion by inducing GSH synthesis and protects epithelial cells by reversing CSE-induced posttranslational modifications of Nrf2. These data may have implications in dietary modulation of antioxidants in treatment of chronic obstructive pulmonary disease.

scholarly journals Flavonoid Fraction of Orange and Bergamot Juices Protect Human Lung Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Nadia Ferlazzo ◽  
Giuseppa Visalli ◽  
Antonella Smeriglio ◽  
Santa Cirmi ◽  
Giovanni Enrico Lombardo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Human Lung ◽  
Antioxidant Properties ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Food Sources ◽  
Plant Metabolites ◽  
Lung Epithelial ◽  
Flavonoid Fraction

It has been reported that oxidant/antioxidant imbalance triggers cell damage that in turn causes a number of lung diseases. Flavonoids are known for their health benefits, andCitrusfruits juices are one of the main food sources of these secondary plant metabolites. The present study was designed to evaluate the effect of the flavonoid fraction of bergamot and orange juices, on H2O2-induced oxidative stress in human lung epithelial A549 cells. First we tested the antioxidant properties of both extracts in cell-free experimental models and then we assayed their capability to prevent the cytotoxic effects induced by H2O2. Our results demonstrated that bothCitrusjuice extracts reduce the generation of reactive oxygen species and membrane lipid peroxidation, improve mitochondrial functionality, and prevent DNA-oxidative damage in A549 cells incubated with H2O2. Our data indicate that the mix of flavonoids present in both bergamot and orange juices may be of use in preventing oxidative cell injury and pave the way for further research into a novel healthy approach to avoid lung disorders.

PM10-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-α

2002 ◽  
Vol 282 (2) ◽  
pp. L237-L248 ◽  
Author(s):  
L. A. Jiménez ◽  
E. M. Drost ◽  
P. S. Gilmour ◽  
I. Rahman ◽  
F. Antonicelli ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
A549 Cells ◽  
Conditioned Media ◽  
Lung Epithelial Cells ◽  
Mrna Levels ◽  
Protein Levels ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Lung Epithelial

There is now considerable evidence for an association between the levels of particulate air pollution [particulate matter <10 μm in aerodynamic diameter (PM10)] and various adverse health endpoints. The release of proinflammatory mediators from PM10-exposed macrophages may be important in stimulating cytokine release from lung epithelial cells, thus amplifying the inflammatory response. A549 cells were treated with conditioned media from monocyte-derived macrophages stimulated with PM10, titanium dioxide (TiO2), or ultrafine TiO2. We demonstrate that only conditioned media from PM10-stimulated macrophages significantly increased nuclear factor-κB and activator protein-1 DNA binding, enhanced interleukin-8 (IL-8) mRNA levels as assessed by RT-PCR, and augmented IL-8 protein levels, over untreated controls. Furthermore, PM10-conditioned media also caused transactivation of IL-8 as determined by an IL-8-chloramphenicol acetyl transferase reporter. Analysis of these conditioned media revealed marked increases in tumor necrosis factor-α (TNF-α) and protein levels and enhanced chemotactic activity for neutrophils. Preincubation of conditioned media with TNF-α-neutralizing antibodies significantly reduced IL-8 production. These data suggest that PM10-activated macrophages may amplify the inflammatory response by enhancing IL-8 release from lung epithelial cells, in part, via elaboration of TNF-α.

scholarly journals Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5091
Author(s):  
Acharya Balkrishna ◽  
Siva Kumar Solleti ◽  
Sudeep Verma ◽  
Anurag Varshney
Keyword(s):  
Herbal Medicine ◽  
High Performance ◽  
Normal Skin ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Spike Protein ◽  
Protective Effects ◽  
Cell Degeneration ◽  
Zebrafish Model ◽  
Tnf Α

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV–V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1β induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.

Sign in / Sign up

Export Citation Format

Share Document