scholarly journals Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1590
Author(s):  
Johanna Berg ◽  
Zia Weber ◽  
Mona Fechler-Bitteti ◽  
Andreas C. Hocke ◽  
Stefan Hippenstiel ◽  
...  
Keyword(s):  
Influenza A ◽  
Human Lung ◽  
Treatment Options ◽  
A549 Cells ◽  
Antiviral Agent ◽  
Lung Model ◽  
Lung Fibroblasts ◽  
Rheological Parameters ◽  
Specific Cell ◽  
Dependent Manner

Influenza A virus (IAV) continuously causes epidemics and claims numerous lives every year. The available treatment options are insufficient and the limited pertinence of animal models for human IAV infections is hampering the development of new therapeutics. Bioprinted tissue models support studying pathogenic mechanisms and pathogen-host interactions in a human micro tissue environment. Here, we describe a human lung model, which consisted of a bioprinted base of primary human lung fibroblasts together with monocytic THP-1 cells, on top of which alveolar epithelial A549 cells were printed. Cells were embedded in a hydrogel consisting of alginate, gelatin and collagen. These constructs were kept in long-term culture for 35 days and their viability, expression of specific cell markers and general rheological parameters were analyzed. When the models were challenged with a combination of the bacterial toxins LPS and ATP, a release of the proinflammatory cytokines IL-1β and IL-8 was observed, confirming that the model can generate an immune response. In virus inhibition assays with the bioprinted lung model, the replication of a seasonal IAV strain was restricted by treatment with an antiviral agent in a dose-dependent manner. The printed lung construct provides an alveolar model to investigate pulmonary pathogenic biology and to support development of new therapeutics not only for IAV, but also for other viruses.

scholarly journals Barium Titanate (BaTiO3) Nanoparticles Exert Cytotoxicity through Oxidative Stress in Human Lung Carcinoma (A549) Cells

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2309
Author(s):  
Maqusood Ahamed ◽  
Mohd Javed Akhtar ◽  
M.A. Majeed Khan ◽  
Hisham A. Alhadlaq ◽  
Aws Alshamsan
Keyword(s):  
Oxidative Stress ◽  
Barium Titanate ◽  
Lung Carcinoma ◽  
Human Lung ◽  
A549 Cells ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Zno Nps ◽  
Human Lung Carcinoma ◽  
Batio3 Nanoparticles

Barium titanate (BaTiO3) nanoparticles (BT NPs) have shown exceptional characteristics such as high dielectric constant and suitable ferro-, piezo-, and pyro-electric properties. Thus, BT NPs have shown potential to be applied in various fields including electro-optical devices and biomedicine. However, very limited knowledge is available on the interaction of BT NPs with human cells. This work was planned to study the interaction of BT NPs with human lung carcinoma (A549) cells. Results showed that BT NPs decreased cell viability in a dose- and time-dependent manner. Depletion of mitochondrial membrane potential and induction of caspase-3 and -9 enzyme activity were also observed following BT NP exposure. BT NPs further induced oxidative stress indicated by induction of pro-oxidants (reactive oxygen species and hydrogen peroxide) and reduction of antioxidants (glutathione and several antioxidant enzymes). Moreover, BT NP-induced cytotoxicity and oxidative stress were effectively abrogated by N-acetyl-cysteine (an ROS scavenger), suggesting that BT NP-induced cytotoxicity was mediated through oxidative stress. Intriguingly, the underlying mechanism of cytotoxicity of BT NPs was similar to the mode of action of ZnO NPs. At the end, we found that BT NPs did not affect the non-cancerous human lung fibroblasts (IMR-90). Altogether, BT NPs selectively induced cytotoxicity in A549 cells via oxidative stress. This work warrants further research on selective cytotoxicity mechanisms of BT NPs in different types of cancer cells and their normal counterparts.

scholarly journals Cytotoxic Effects of Flubendazole in Human Lung Cancer Cell Line A549

2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Elham Hoveizi ◽  
Fatemeh Fakharzadeh Jahromi
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Human Lung ◽  
A549 Cells ◽  
Beclin 1 ◽  
Human Lung Cancer ◽  
Pcr Analysis ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Acridine Orange Staining

Background: The development of effective anticancer drugs is a significant health issue. Previous studies showed that members of the benzimidazole family have anticancer effects on several cancers Objectives: The present study investigated the cytotoxic effect of flubendazole on A549 human lung cancer cells. Methods: The A549 cells were treated with flubendazole at 1, 2, 5, and 10 µM concentrations for three days. Cell viability was measured by the MTT assay and Acridine orange staining. Also, the expressions of P62 and Beclin -1 were analyzed by qRT-PCR analysis. Results: Cell viability of A549 cells, in a concentration-dependent manner, showed significant differences between the treatment and control groups, and the IC50 value was determined to be 2 µM. Also, flubendazole reduced the expression of P62 and increased the expression of Beclin 1 in treated cells. Conclusions: Flubendazole induces cell death in A549 cells in a dose and time-dependent manner and can offer new factors in lung cancer therapeutic strategies.

TNF-± Induces TSLP Expression By Human Lung Fibroblasts In An AP-1 / JNK Dependent Manner

2010 ◽  
Author(s):  
Arnab Datta ◽  
Chris J. Scotton ◽  
Alejandro Ortiz-Stern ◽  
Robin J. McAnulty ◽  
Rachel C. Chambers
Keyword(s):  
Human Lung ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Human Lung Fibroblasts

TGF-β1 Induces Tissue Factor Expression in Human Lung Fibroblasts in a PI3K/JNK/Akt-Dependent and AP-1–Dependent Manner

2012 ◽  
Vol 47 (5) ◽  
pp. 614-627 ◽  
Author(s):  
Malgorzata Wygrecka ◽  
Dariusz Zakrzewicz ◽  
Brigitte Taborski ◽  
Miroslava Didiasova ◽  
Grazyna Kwapiszewska ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Human Lung Fibroblasts ◽  
Factor Expression ◽  
Tgf Β1

Extract from the Leaves of Toona sinensis Roemor Exerts Potent Antiproliferative Effect on Human Lung Cancer Cells

2002 ◽  
Vol 30 (02n03) ◽  
pp. 307-314 ◽  
Author(s):  
Hui-Chiu Chang ◽  
Wen-Chun Hung ◽  
Ming-Shyan Huang ◽  
Hseng-Kuang Hsu
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Lung Fibroblasts ◽  
Human Lung Cancer ◽  
Toona Sinensis

Recent study indicated that the components of Toona sinensis Roemor have potent anti-inflammatory and analgesic effects. These components have also been reported to inhibit the growth of boils in vivo. In this study, we investigated the effect of crude extract from the leaves of Toona sinensis Roemor on the proliferation of A549 lung cancer cells. We found that the extract effectively blocked cell cycle progression by inhibiting the expression of cyclin D1 and E in A549 cells. Additionally, incubation of the extract led to activation of caspase-3-like proteases and apoptotic cell death. Conversely, the extract did not show any significant cytotoxic effect on primarily cultured human foreskin fibroblasts or MRC-5 human lung fibroblasts. Therefore, antiproliferative action of the extract is specific for tumor cells. Our results suggest that the components of Toona sinensis Roemor have potent anticancer effects in vitro and identification of the useful components in the extract may lead to the development of a novel class of anticancer drugs.

scholarly journals Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor.

1996 ◽  
Vol 184 (1) ◽  
pp. 191-201 ◽  
Author(s):  
M Roth ◽  
M Nauck ◽  
S Yousefi ◽  
M Tamm ◽  
K Blaser ◽  
...  
Keyword(s):  
Pertussis Toxin ◽  
Tyrosine Kinases ◽  
Human Lung ◽  
Human Fibroblasts ◽  
Platelet Activating Factor ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Human Lung Fibroblasts ◽  
Paf Receptor

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator of the lung. In this study, we demonstrate that PAF receptor mRNA and protein is expressed by human lung fibroblasts. Interaction of PAF with its specific receptor resulted in increases of tyrosine phosphorylation of several intracellular proteins, indicating that the PAF-receptor might be functionally active. PAF-induced transcription of protooncogenes c-fos and c-jun as well as of interleukin (IL)-6 and IL-8 genes in human fibroblasts. Transcription of the interleukins was followed by secretion of the respective proteins. Moreover, PAF enhanced proliferation of fibroblasts in a concentration-dependent manner. Using signaling inhibitors, we demonstrate that PAF-induced transcription of the c-fos, IL-6, and IL-8 genes, as well as proliferation, require activation of pertussis toxin-sensitive G proteins, tyrosine kinases, and protein kinase C (PKC). In contrast, transcription of c-jun was blocked by pertussis toxin, but not by inhibitors for tyrosine kinases or PKC. These data suggest that PAF stimulates distinct signaling pathways in human lung fibroblasts. In addition, the activation of human fibroblasts by PAF leads to enhanced proliferation and to the expression of proinflammatory cytokines, which may contribute to the pathophysiological changes in pulmonary inflammation.

scholarly journals Investigation of Cytotoxicity Apoptotic and Inflammatory Responses of Biosynthesized Zinc Oxide Nanoparticles from Ocimum sanctum Linn in Human Skin Keratinocyte (Hacat) and Human Lung Epithelial (A549) Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bader Almutairi ◽  
Gadah Albahser ◽  
Rafa Almeer ◽  
Nouf M. Alyami ◽  
Hanouf Almukhlafi ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Human Skin ◽  
Zinc Oxide Nanoparticles ◽  
Human Lung ◽  
A549 Cells ◽  
Ocimum Sanctum ◽  
Oxide Nanoparticles ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Lung Epithelial

Pristine and engineered metal nanoparticles are widely applied in various fields of industry, and as consequences, they are useful as well as harmful to human health and environment. This study aimed at synthesizing the green zinc oxide nanoparticles (ZnNPs) using the leaf extract of Ocimum sanctum Linn and assessing its toxicity on human skin epidermal (HaCaT) and human lung epithelial (A549) cells. The synthesized green ZnNPs (gZnNPs) were characterized by using dynamic light scattering (DLS) and a high-resolution transmission electron microscope. The average size of gZnNPs obtained was 62 nm with a spherical shape. The effects of gZnNPs on the viability of HaCaT and A549 cells were investigated using tetrazolium salt (MTT) for 24 h. We have seen more reduction of cell viability of A549 cells in comparison to HaCaT cells. The induction of intracellular reactive oxygen species (ROS) was measured using DCFDA assay and showed a slightly high intensity of green fluorescence in A549 than HaCaT cells. The different oxidative stress biomarkers such as ROS generation and lipid peroxide were increased, and GSH was decreased in a dose-dependent manner. The apoptotic and necrotic effect of gZnNPs in both cells was carried out using Annexin-V-FITC and propidium iodide staining. More apoptotic and necrotic cells were found at a higher concentration of gZnNPs exposure. Also, we determined the effect of gZnNPs at the molecular level by evaluating the apoptotic and inflammatory markers, in which gZnNPs downregulated Bcl2 and upregulated Bax, caspase-3, and TNF-α in HaCaT and A549 cells. Ultimately, gZnNPs exerted toxicity and apoptosis in HaCaT and A549 cells.

Glucocorticoid-induced contractility and F-actin content of human lung fibroblasts in three-dimensional culture

2000 ◽  
Vol 278 (1) ◽  
pp. L13-L18 ◽  
Author(s):  
Hiroyuki Miki ◽  
Tadashi Mio ◽  
Sonoko Nagai ◽  
Yuma Hoshino ◽  
Takeo Tsutsumi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Human Lung ◽  
Healing Process ◽  
Lung Fibroblast ◽  
Lung Fibroblasts ◽  
Wound Healing Process ◽  
Architectural Distortion ◽  
Type I ◽  
Dependent Manner ◽  
Human Lung Fibroblast

Fibroblast contractility plays a useful role in the wound healing process but contributes to architectural distortion in the lungs. Glucocorticoids (GCs) have been reported to reduce dermal fibroblast contractility, which may result in delaying wound healing, but the effects on lung fibroblasts are unknown. In this study, we examined how human lung fibroblast contractility is altered in the presence of GCs. Lung fibroblast cell lines ( n = 5) were established from normal parts of surgically resected lung tissue. The effects of GCs on contractility were investigated with a type I collagen gel contraction assay. Filamentous actin (F-actin) content was detected by confocal microscopy and measured with a fluorescent phalloidin binding assay. GCs augmented fibroblast contraction in a concentration-dependent manner, with an approximate EC50 of 1.8 × 10−8 M, whereas other steroid derivatives had no effects. GC contractility needed de novo protein synthesis. The GC-induced increase in contractility was found to be consistent with an increase in F-actin content. In conclusion, lung fibroblast contractility was enhanced with GCs through an upregulation of lung fibroblast F-actin.

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