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 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.

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.

A model to identify novel targets involved in oxidative stress-induced apoptosis in human lung epithelial cells by RNA interference

2010 ◽  
Vol 24 (1) ◽  
pp. 310-318 ◽  
Author(s):  
William E. Wixted ◽  
Chris Kitson ◽  
Jayne C. Colebrook ◽  
Emma J. Roberts ◽  
Steven M. Fox ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rna Interference ◽  
Epithelial Cells ◽  
Human Lung ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Novel Targets ◽  
Induced Apoptosis ◽  
Human Lung Epithelial Cells

Ionizing radiation enhances matrix metalloproteinase-2 production in human lung epithelial cells

2001 ◽  
Vol 280 (1) ◽  
pp. L30-L38 ◽  
Author(s):  
Jun Araya ◽  
Muneharu Maruyama ◽  
Kazuhiko Sassa ◽  
Tadashi Fujita ◽  
Ryuji Hayashi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ionizing Radiation ◽  
Basement Membrane ◽  
Lung Injury ◽  
Human Lung ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Radiation Induced ◽  
Human Lung Epithelial Cells

Radiation pneumonitis is a major complication of radiation therapy. However, the detailed cellular mechanisms have not been clearly defined. Based on the recognition that basement membrane disruption occurs in acute lung injury and that matrix metalloproteinase (MMP)-2 can degrade type IV collagen, one of the major components of the basement membrane, we hypothesized that ionizing radiation would modulate MMP-2 production in human lung epithelial cells. To evaluate this, the modulation of MMP-2 with irradiation was investigated in normal human bronchial epithelial cells as well as in A549 cells. We measured the activity of MMP-2 in the conditioned medium with zymography and the MMP-2 mRNA level with RT-PCR. Both of these cells constitutively expressed 72-kDa gelatinolytic activity, corresponding to MMP-2, and exposure to radiation increased this activity. Consistent with the data of zymography, ionizing radiation increased the level of MMP-2 mRNA. This radiation-induced increase in MMP-2 expression was mediated via p53 because the p53 antisense oligonucleotide abolished the increase in MMP-2 activity as well as the accumulation of p53 after irradiation in A549 cells. These results indicate that MMP-2 expression by human lung epithelial cells is involved in radiation-induced lung injury.

scholarly journals TRIM28 regulates SARS-CoV-2 cell entry by targeting ACE2

2020 ◽  
Author(s):  
Yinfang Wang ◽  
Yingzhe Fan ◽  
Yitong Huang ◽  
Tao Du ◽  
Zongjun Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nk Cells ◽  
Interleukin 2 ◽  
A549 Cells ◽  
Endogenous Retrovirus ◽  
Alveolar Epithelial Cells ◽  
Cell Entry ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Ifn Γ

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), it binds to angiotensin-converting enzyme 2 (ACE2) to enter into human cells. The expression level of ACE2 potentially determine the susceptibility and severity of COVID-19, it is thus of importance to understand the regulatory mechanism of ACE2 expression. Tripartite motif containing 28 (TRIM28) is known to be involved in multiple processes including antiviral restriction, endogenous retrovirus latency and immune response, it is recently reported to be co-expressed with SARS-CoV-2 receptor in type II pneumocytes; however, the roles of TRIM28 in ACE2 expression and SARS-CoV-2 cell entry remain unclear. This study showed that knockdown of TRIM28 induces ACE2 expression and increases pseudotyped SARS-CoV-2 cell entry of A549 cells and primary pulmonary alveolar epithelial cells (PAEpiCs). In a co-culture model of NK cells and lung epithelial cells, our results demonstrated that NK cells inhibit TRIM28 and promote ACE2 expression in lung epithelial cells, which was partially reversed by depletion of interleukin-2 and blocking of granzyme B in the co-culture medium. Furthermore, TRIM28 knockdown enhanced interferon-γ (IFN-γ)-induced ACE2 expression through a mechanism involving upregulating IFN-γ receptor 2 (IFNGR2) in both A549 and PAEpiCs. Importantly, the upregulated ACE2 induced by TRIM28 knockdown and co-culture of NK cells was partially reversed by dexamethasone in A549 cells but not PAEpiCs. Our study identified TRIM28 as a novel regulator of ACE2 expression and SARS-CoV-2 cell entry.

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