Journal articles: 'A549-Thp-1'

1

Qin, Y., P. Zhao, Y. Chen, X. Liu, H. Dong, W. Zheng, C. Li, X. Mao, and J. Li. "Lipopolysaccharide induces epithelial–mesenchymal transition of alveolar epithelial cells cocultured with macrophages possibly via the JAK2/STAT3 signaling pathway." Human & Experimental Toxicology 39, no. 2 (October 14, 2019): 224–34. http://dx.doi.org/10.1177/0960327119881678.

Full text

Abstract:

Epithelial–mesenchymal transition (EMT) plays a key role in the process of pulmonary fibrosis (PF). Increasing evidences have shown that exaggerated EMT in recurrent pulmonary injury mediates the early pathogenesis of PF. This study aimed to evaluate EMT of human alveolar epithelial cells (A549) when cocultured with human macrophages Tohoku hospital pediatrics-1 (THP-1) induced by lipopolysaccharide (LPS) and investigate the role of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Firstly, we detected the inflammatory and EMT biomarkers in A549 cells monoculture and A549/THP-1 cells coculture in the presence or absence of LPS. Then, the activation of JAK2/STAT3 signaling pathway was determined in coculture. Interestingly, inflammatory markers, such as interleukin (IL)-6, matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)- β, and collagen type 1 (COL-1), were enhanced in LPS treated coculture. Besides, the expression of E-cadherin decreased but α-smooth muscle actin expression increased, indicating the presence of EMT in A549 cells when cocultured with THP-1 macrophages. However, these phenotypes could not be observed in LPS-treated A549 cells monoculture. Meanwhile, JAK2/STAT3 signaling pathway was activated, and the STAT3 DNA-binding and inflammatory markers were inhibited by Stattic. Together, these findings demonstrate the key role of JAK2/STAT3 signaling pathway in LPS promoted EMT of A549 in the presence of THP-1 macrophages as an in vitro PF model.

APA, Harvard, Vancouver, ISO, and other styles

2

Hirst, Robert A., Hasan Yesilkaya, Edwin Clitheroe, Andrew Rutman, Nichola Dufty, Timothy J. Mitchell, Christopher O’Callaghan, and Peter W. Andrew. "Sensitivities of Human Monocytes and Epithelial Cells to Pneumolysin Are Different." Infection and Immunity 70, no. 2 (February 2002): 1017–22. http://dx.doi.org/10.1128/iai.70.2.1017-1022.2002.

Full text

Abstract:

ABSTRACT The Streptococcus pneumoniae pore-forming toxin, pneumolysin, is an important virulence factor in pneumococcal pneumonia. The effect of pneumolysin on human lung epithelial and monocyte cell viability was compared. Pneumolysin caused a dose-dependent loss of viability of human lung epithelial (A549 and L132) and monocyte (U937 and THP-1) cell lines. Analysis of the dose-response curves revealed similar log 50% inhibitory concentration (pIC50) values for A549, L132, and THP-1 of 0.12± 0.1, 0.02± 0.04, and 0.12± 0.13 hemolytic units (HU), respectively, but U937 cells showed a significantly greater pIC50 of 0.42± 0.12 HU. Differentiation of A549 and L132 with phorbol ester or THP-1 with gamma interferon had no effect on their sensitivity to pneumolysin. However, a significant decrease in the potency of pneumolysin against U937 cells followed gamma interferon treatment. The Hill slopes of the inhibition curves were greater than unity, indicating that pneumolysin may act with positive cooperativity. Analysis of pneumolysin-treated THP-1 cells by electron microscopy revealed membrane lesions of between 100 and 200 nm in diameter.

APA, Harvard, Vancouver, ISO, and other styles

3

Venugopal, Rajanbabu, Lakshmi Galam, Ruan Cox, Jutaro Fukumoto, Young Cho, Prasanna Tamarapu Parthasarathy, Richard F. Lockey, and Narasaiah Kolliputi. "Inflammasome Inhibition Suppresses Alveolar Cell Permeability Through Retention of Neuregulin-1 (NRG-1)." Cellular Physiology and Biochemistry 36, no. 5 (2015): 2012–24. http://dx.doi.org/10.1159/000430169.

Full text

Abstract:

Background: Neuregulin (NRG)-1-human epidermal receptor (HER)-2 signaling pathway is a key regulator of IL-1β-mediated pulmonary inflammation and epithelial permeability. The inflammasome is a newly discovered molecular platform required for caspase-1 activation and maturation of IL-1β. However, the role of the inflammasome in NRG-1-HER2 signaling-mediated alveolar cell permeability is unknown. Methods: The inflammasome was activated or inhibited in THP-1 cells; supernatants from these cells were added to A549 cells and human small airway epithelial cells (HSAEC). The protein expression of NRG-1 and phospho-HER2 (pHER2) were measured by Western blot analysis and epithelial permeability was measured using Lucifer yellow dye. Results: Results reveal that alveolar permeability in A549 cells and HSAEC is increased when treated with supernatants of inflammasome-activated THP-1 cells. Alveolar permeability is significantly suppressed when treated with supernatant of inflammasome-inhibited THP-1 cells. Inflammasome-mediated permeability is decreased when A549 cells and HSAEC are pretreated with IL-1β receptor antagonist (IL-1βRA). In addition, HER2 kinase inhibitor AG825 or NRG-1 inhibitor TAPI inhibits inflammasome-mediated permeability in A549 cells and HSAEC demonstrating critical roles of IL-1β, NRG-1, and HER2 in inflammasome-mediated alveolar permeability. Conclusion: These findings suggest that inflammasome-induced alveolar cell permeability is mediated by NRG-1/HER2 signaling through IL-1β regulation.

APA, Harvard, Vancouver, ISO, and other styles

4

Ge, Lingqing, Qiaozhen Hu, Mengrao Shi, Huiyun Yang, and Guoji Zhu. "Design and discovery of novel thiazole derivatives as potential MMP inhibitors to protect against acute lung injury in sepsis rats via attenuation of inflammation and apoptotic oxidative stress." RSC Advances 7, no. 52 (2017): 32909–22. http://dx.doi.org/10.1039/c7ra03511j.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Jakšić, Daniela, Dubravko Jelić, Nevenka Kopjar, and Maja Šegvić Klarić. "Combined Toxicity of the Most Common Indoor Aspergilli." Pathogens 12, no. 3 (March 14, 2023): 459. http://dx.doi.org/10.3390/pathogens12030459.

Full text

Abstract:

The most common Aspergilli isolated from indoor air samples from occupied buildings and a grain mill were extracted and analyzed for their combined (Flavi + Nigri, Versicolores + Nigri) cytotoxic, genotoxic and pro-inflammatory properties on human adenocarcinoma cells (A549) and monocytic leukemia cells induced in macrophages (THP-1 macrophages). Metabolite mixtures from the Aspergilli series Nigri increase the cytotoxic and genotoxic potency of Flavi extracts in A549 cells suggesting additive and/or synergistic effects, while antagonizing the cytotoxic potency of Versicolores extracts in THP-1 macrophages and genotoxicity in A549 cells. All tested combinations significantly decreased IL-5 and IL-17, while IL-1β, TNF-α and IL-6 relative concentrations were increased. Exploring the toxicity of extracted Aspergilli deepens the understanding of intersections and interspecies differences in events of chronic exposure to their inhalable mycoparticles.

APA, Harvard, Vancouver, ISO, and other styles

6

Meindl, Claudia, Kristin Öhlinger, Verena Zrim, Thomas Steinkogler, and Eleonore Fröhlich. "Screening for Effects of Inhaled Nanoparticles in Cell Culture Models for Prolonged Exposure." Nanomaterials 11, no. 3 (February 28, 2021): 606. http://dx.doi.org/10.3390/nano11030606.

Full text

Abstract:

Respiratory exposure of humans to environmental and therapeutic nanoparticles repeatedly occurs at relatively low concentrations. To identify adverse effects of particle accumulation under realistic conditions, monocultures of Calu-3 and A549 cells and co-cultures of A549 and THP-1 macrophages in the air–liquid interphase culture were exposed repeatedly to 2 µg/cm2 20 nm and 200 nm polystyrene particles with different functionalization. Particle accumulation, transepithelial electrical resistance, dextran (3–70 kDa) uptake and proinflammatory cytokine secretion were determined over 28 days. Calu-3 cells showed constant particle uptake without any change in barrier function and cytokine release. A549 cells preferentially ingested amino- and not-functionalized particles combined with decreased endocytosis. Cytokine release was transiently increased upon exposure to all particles. Carboxyl-functionalized demonstrated higher uptake and higher cytokine release than the other particles in the A549/THP-1 co-cultures. The evaluated respiratory cells and co-cultures ingested different amounts and types of particles and caused small (partly transient) effects. The data suggest that the healthy cells can adapt to low doses of non-cytotoxic particles.

APA, Harvard, Vancouver, ISO, and other styles

7

Yen, Yu-Ting, Fang Liao, Cheng-Hsiang Hsiao, Chuan-Liang Kao, Yee-Chun Chen, and Betty A. Wu-Hsieh. "Modeling the Early Events of Severe Acute Respiratory Syndrome Coronavirus Infection In Vitro." Journal of Virology 80, no. 6 (March 15, 2006): 2684–93. http://dx.doi.org/10.1128/jvi.80.6.2684-2693.2006.

Full text

Abstract:

ABSTRACT The clinical picture of severe acute respiratory syndrome (SARS) is characterized by pulmonary inflammation and respiratory failure, resembling that of acute respiratory distress syndrome. However, the events that lead to the recruitment of leukocytes are poorly understood. To study the cellular response in the acute phase of SARS coronavirus (SARS-CoV)-host cell interaction, we investigated the induction of chemokines, adhesion molecules, and DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin) by SARS-CoV. Immunohistochemistry revealed neutrophil, macrophage, and CD8 T-cell infiltration in the lung autopsy of a SARS patient who died during the acute phase of illness. Additionally, pneumocytes and macrophages in the patient's lung expressed P-selectin and DC-SIGN. In in vitro study, we showed that the A549 and THP-1 cell lines were susceptible to SARS-CoV. A549 cells produced CCL2/monocyte chemoattractant protein 1 (MCP-1) and CXCL8/interleukin-8 (IL-8) after interaction with SARS-CoV and expressed P-selectin and VCAM-1. Moreover, SARS-CoV induced THP-1 cells to express CCL2/MCP-1, CXCL8/IL-8, CCL3/MIP-1α, CXCL10/IP-10, CCL4/MIP-1β, and CCL5/RANTES, which attracted neutrophils, monocytes, and activated T cells in a chemotaxis assay. We also demonstrated that DC-SIGN was inducible in THP-1 as well as A549 cells after SARS-CoV infection. Our in vitro experiments modeling infection in humans together with the study of a lung biopsy of a patient who died during the early phase of infection demonstrated that SARS-CoV, through a dynamic interaction with lung epithelial cells and monocytic cells, creates an environment conducive for immune cell migration and accumulation that eventually leads to lung injury.

APA, Harvard, Vancouver, ISO, and other styles

8

Jin, Lilan, Lu Deng, Mark Bartlett, Yiping Ren, Jihong Lu, Qian Chen, Yixiao Pan, Hai Wang, Xiaokui Guo, and Chang Liu. "A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier." Nutrients 14, no. 10 (May 11, 2022): 2010. http://dx.doi.org/10.3390/nu14102010.

Full text

Abstract:

Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.

APA, Harvard, Vancouver, ISO, and other styles

9

Zhang, Lemeng, Huifang Yi, Jianhua Chen, Haitao Li, Yongzhong Luo, Tianli Cheng, Hua Yang, Zhou Jiang, and Changqie Pan. "Neutrophil Extracellular Traps Facilitate A549 Cell Invasion and Migration in a Macrophage-Maintained Inflammatory Microenvironment." BioMed Research International 2022 (January 6, 2022): 1–11. http://dx.doi.org/10.1155/2022/8316525.

Full text

Abstract:

Introduction. The biological functions of neutrophil extracellular traps (NETs) in tumorigenesis have drawn an increasing amount of attention. This study explored the relationship between NETs and the inflammatory microenvironment in lung cancer cell invasion and metastasis. Methods. NETs were quantified using myeloperoxidase (MPO–DNA) and immunofluorescence staining. Cytokine levels were measured using ELISA kits. THP-1 and A549 cells were used for in vitro experiments. Transwell and Matrigel assays were used to assess the invasion and migration abilities of the cells. Results. Neutrophil infiltration and NET formation were observed in the lung cancer tissues. Compared with healthy controls, the level of MPO–DNA complexes in lung cancer patients increased remarkably and was positively correlated with peripheral blood neutrophil counts, smoking status, and poor prognosis. Increased circulating NET levels were also positively correlated with the levels of inflammatory cytokines, including IL-1β, IL-6, IL-18, and TNF-α. Neutrophils isolated from patients with lung cancer are more prone to NET release. NETs can promote the invasion and migration ability of THP-1 and A549 cell in coculture systems, while pretreatment with NET inhibitors can effectively reduce NET-induced invasion and metastasis. The ability of NETs to promote invasion and metastasis is partly dependent on macrophages. Conclusion. Taken together, our study demonstrated that NETs facilitate A549 cell invasion and migration in a macrophage-maintained inflammatory microenvironment.

APA, Harvard, Vancouver, ISO, and other styles

10

Mejía-Méndez, Jorge L., Ana C. Lorenzo-Leal, Horacio Bach, Edgar R. López-Mena, Diego E. Navarro-López, Luis R. Hernández, Zaida N. Juárez, and Eugenio Sánchez-Arreola. "Antimicrobial, Cytotoxic, and Anti-Inflammatory Activities of Tigridia vanhouttei Extracts." Plants 12, no. 17 (August 31, 2023): 3136. http://dx.doi.org/10.3390/plants12173136.

Full text

Abstract:

In this work, bulb extracts of Tigridia vanhouttei were obtained by maceration with solvents of increasing polarity. The extracts were evaluated against a panel of pathogenic bacterial and fungal strains using the minimal inhibitory concentration (MIC) assay. The cytotoxicity of the extracts was tested against two cell lines (THP-1 and A549) using the MTT assay. The anti-inflammatory activity of the extracts was evaluated in THP-1 cells by measuring the secretion of pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines by ELISA. The chemical composition of the extracts was recorded by FTIR spectroscopy, and their chemical profiles were evaluated using GC-MS. The results revealed that only hexane extract inhibited the growth of the clinical isolate of Pseudomonas aeruginosa at 200 μg/mL. Against THP-1 cells, hexane and chloroform extracts were moderately cytotoxic, as they exhibited LC50 values of 90.16, and 46.42 μg/mL, respectively. Treatment with methanol extract was weakly cytotoxic at LC50 443.12 μg/mL against the same cell line. Against the A549 cell line, hexane, chloroform, and methanol extracts were weakly cytotoxic because of their LC50 values: 294.77, 1472.37, and 843.12 μg/mL. The FTIR analysis suggested the presence of natural products were confirmed by carboxylic acids, ketones, hydroxyl groups, or esters. The GC-MS profile of extracts revealed the presence of phytosterols, tetracyclic triterpenes, multiple fatty acids, and sugars. This report confirms the antimicrobial, cytotoxic, and anti-inflammatory activities of T. vanhouttei.

APA, Harvard, Vancouver, ISO, and other styles

11

Boggaram, Vijay, David S. Loose, Koteswara R. Gottipati, Kartiga Natarajan, and Courtney T. Mitchell. "Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory and immune response genes." Physiological Genomics 48, no. 4 (April 2016): 281–89. http://dx.doi.org/10.1152/physiolgenomics.00096.2015.

Full text

Abstract:

The intensification and concentration of animal production operations expose workers to high levels of organic dusts in the work environment. Exposure to organic dusts is a risk factor for the development of acute and chronic respiratory symptoms and diseases. Lung epithelium plays important roles in the control of immune and inflammatory responses to environmental agents to maintain lung health. To better understand the effects of organic dust on lung inflammatory responses, we characterized the gene expression profiles of A549 alveolar and Beas2B bronchial epithelial and THP-1 monocytic cells influenced by exposure to poultry dust extract by DNA microarray analysis using Illumina Human HT-12 v4 Expression BeadChip. We found that A549 alveolar and Beas2B bronchial epithelial and THP-1 cells responded with unique changes in the gene expression profiles with regulation of genes encoding inflammatory cytokines, chemokines, and other inflammatory proteins being common to all the three cells. Significantly induced genes included IL-8, IL-6, IL-1β, ICAM-1, CCL2, CCL5, TLR4, and PTGS2. Validation by real-time qRT-PCR, ELISA, Western immunoblotting, and immunohistochemical staining of lung sections from mice exposed to dust extract validated DNA microarray results. Pathway analysis indicated that dust extract induced changes in gene expression influenced functions related to cellular growth and proliferation, cell death and survival, and cellular development. These data show that a broad range of inflammatory mediators produced in response to poultry dust exposure can modulate lung immune and inflammatory responses. This is the first report on organic dust induced changes in expression profiles in lung epithelial and THP-1 monocytic cells.

APA, Harvard, Vancouver, ISO, and other styles

12

Jiang, Lin-Lin, Jin-Xiu Tang, Yong-Heng Bo, You-Zhi Li, Tao Feng, Hong-Wei Zhu, Xin Yu, Xing-Xiao Zhang, Jian-Long Zhang, and Weiyi Wang. "Cytotoxic Secondary Metabolites Isolated from the Marine Alga-Associated Fungus Penicillium chrysogenum LD-201810." Marine Drugs 18, no. 5 (May 22, 2020): 276. http://dx.doi.org/10.3390/md18050276.

Full text

Abstract:

A new pentaketide derivative, penilactonol A (1), and two new hydroxyphenylacetic acid derivatives, (2’R)-stachyline B (2) and (2’R)-westerdijkin A (3), together with five known metabolites, bisabolane-type sesquiterpenoids 4–6 and meroterpenoids 7 and 8, were isolated from the solid culture of a marine alga-associated fungus Penicillium chrysogenum LD-201810. Their structures were elucidated based on extensive spectroscopic analyses, including 1D/2D NMR and high resolution electrospray ionization mass spectra (HRESIMS). The absolute configurations of the stereogenic carbons in 1 were determined by the (Mo2(OAc)4)-induced circular dichroism (CD) and comparison of the calculated and experimental electronic circular dichroism (ECD) spectra, while the absolute configuration of the stereogenic carbon in 2 was established using single-crystal X-ray diffraction analysis. Compounds 2 and 3 adapt the 2’R-configuration as compared to known hydroxyphenylacetic acid-derived and O-prenylated natural products. The cytotoxicity of 1–8 against human carcinoma cell lines (A549, BT-549, HeLa, HepG2, MCF-7, and THP-1) was evaluated. Compound 3 exhibited cytotoxicity to the HepG2 cell line with an IC50 value of 22.0 μM. Furthermore, 5 showed considerable activities against A549 and THP-1 cell lines with IC50 values of 21.2 and 18.2 μM, respectively.

APA, Harvard, Vancouver, ISO, and other styles

13

Altube, María Julia, Ezequiel Nicolás Caputo, Martín Nicolás Rivero, María Laura Gutiérrez, and Eder Lilia Romero. "Photodynamic Therapy with Nebulized Nanocurcumin on A549 Cells, Model Vessels, Macrophages and Beyond." Pharmaceutics 14, no. 12 (November 29, 2022): 2637. http://dx.doi.org/10.3390/pharmaceutics14122637.

Full text

Abstract:

This study aimed to determine the damage mechanisms caused by naturally targeted nanoarchaeosomes made of diether lipids from Halorubrum tebenquichense loaded with curcumin (CUR, nATC), which mediated photodynamic therapy (PDT) on A549 cells and on THP-1-macrophages, two cell types found in airway cancers. The effect of nATC- PDT on vessels modeled with a chicken embryo chorioallantoic membrane (CAM), after dropping the formulations on its surface covered with mucins, was also determined. nATCs are known to efficiently trap CUR for at least six months, constituting easy-to-prepare, stable formulations suitable for nebulization. CUR instead, is easily released from carriers such as liposomes made of ordinary phospholipids and cholesterol after a few weeks. Irradiated at 9 J/cm2, nATC (made of archaeolipids: Tween 80: CUR at 1:0.4:0.04 w:w, size 180 ± 40 nm, ζ potential −24 mV, 150 μg CUR/15 mg lipids/mL) was phototoxic (3.7 ± 0.5 μM IC50), on A549 cells after 24 h. The irradiation reduced mitochondrial membrane potential (ΔΨm), ATP levels and lysosomal functionalism, and caused early apoptotic death and late necrosis of A549 cells upon 24 h. nATC induced higher extra and intracellular reactive oxygen species (ROS) than free CUR. nATC-PDT impaired the migration of A549 cells in a wound healing assay, reduced the expression of CD204 in THP-1 macrophages, and induced the highest levels of IL-6 and IL-8, suggesting a switch of macrophage phenotype from pro-tumoral M2 to antitumoral M1. Moreover, nATC reduced the matrix metalloproteinases (MMP), −2 and −9 secretion, by A549 cells with independence of irradiation. Finally, remarkably, upon irradiation at 9 J/cm2 on the superficial vasculature of a CAM covered with mucins, nATC caused the vessels to collapse after 8 h, with no harm on non-irradiated zones. Overall, these results suggest that nebulized nATC blue light-mediated PDT may be selectively deleterious on superficial tumors submerged under a thick mucin layer.

APA, Harvard, Vancouver, ISO, and other styles

14

Jeon, Soyeon, Jessica Clavadetscher, Dong-Keun Lee, Sunay Chankeshwara, Mark Bradley, and Wan-Seob Cho. "Surface Charge-Dependent Cellular Uptake of Polystyrene Nanoparticles." Nanomaterials 8, no. 12 (December 10, 2018): 1028. http://dx.doi.org/10.3390/nano8121028.

Full text

Abstract:

The evaluation of the role of physicochemical properties in the toxicity of nanoparticles is important for the understanding of toxicity mechanisms and for controlling the behavior of nanoparticles. The surface charge of nanoparticles is suggested as one of the key parameters which decide their biological impact. In this study, we synthesized fluorophore-conjugated polystyrene nanoparticles (F-PLNPs), with seven different types of surface functional groups that were all based on an identical core, to evaluate the role of surface charge in the cellular uptake of nanoparticles. Phagocytic differentiated THP-1 cells or non-phagocytic A549 cells were incubated with F-PLNP for 4 h, and their cellular uptake was quantified by fluorescence intensity and confocal microscopy. The amount of internalized F-PLNPs showed a good positive correlation with the zeta potential of F-PLNPs in both cell lines (Pearson’s r = 0.7021 and 0.7852 for zeta potential vs. cellular uptake in THP-1 cells and nonphagocytic A549 cells, respectively). This result implies that surface charge is the major parameter determining cellular uptake efficiency, although other factors such as aggregation/agglomeration, protein corona formation, and compositional elements can also influence the cellular uptake partly or indirectly.

APA, Harvard, Vancouver, ISO, and other styles

15

Horie, Masanori, Haruhisa Kato, Shigehisa Endoh, Ayako Nakamura, Junko Maru, Naohide Shinohara, and Katsuhide Fujita. "Effects of Various Carbon Nanotube Suspensions on A549, THP-1, and Peritoneal Macrophage Cells." Journal of Biomimetics, Biomaterials and Biomedical Engineering 24 (July 2015): 1–13. http://dx.doi.org/10.4028/www.scientific.net/jbbbe.24.1.

Full text

Abstract:

The effects of iron content, fiber length, and stability of carbon nanotube (CNT) suspension on cells were examined. Five kinds of single-wall carbon nanotube (SWCNT) suspensions were prepared: with catalytic iron, without iron, long SWCNTs (stable), short SWCNTs (stable), and short SWCNT (unstable). These suspensions were applied to A549, THP-1, and mouse peritoneal macrophage cells. After a 24-h exposure, the mitochondrial activity, cell membrane damage, intracellular oxidative stress, and expression of cytokine genes were determined. Among these properties of SWCNTs, stability of CNT suspension had the most influence on the cells, whereas the effects of iron content and fiber length were small. The unstable SWCNT suspension caused a substantial increase in intracellular ROS levels. Additionally, the cellular effects of stable multi-wall carbon nanotubes (MWCNTs) were examined. The MWCNT suspension did not show any cellular effects. Overall, influences of CNT suspension on mitochondrial activity and cell membrane damage were small. These results suggest that the physical properties of CNT suspension are important factors for their cellular effects. Thus, CNT suspensions prepared with the same material but having different physical properties would differ in the cellular effects they exert, including cytotoxicity. Therefore, physical characterization of CNT suspensions is essential to the evaluation of CNT toxicity. In particular, stability of CNT suspension notably influenced the intracellular ROS level.

APA, Harvard, Vancouver, ISO, and other styles

16

Bredeck, Gerrit, Mathias Busch, Andrea Rossi, Burkhard Stahlmecke, Khanneh Wadinga Fomba, Hartmut Herrmann, and Roel P. F. Schins. "72 Endotoxin Exacerbates the NLRP3-Dependent Inflammatory Potency of Saharan Dust." Annals of Work Exposures and Health 67, Supplement_1 (May 1, 2023): i56. http://dx.doi.org/10.1093/annweh/wxac087.135.

Full text

Abstract:

Abstract Epidemiological studies have shown that desert dust exposure affects respiratory health. We aimed to investigate the NLRP3 inflammasome-caspase-1 pathway-dependent inflammatory properties of Saharan dust (SD) in a macrophage model and an air-liquid interface (ALI) co-culture model of the alveolar epithelium. Under submerged conditions wild-type (WT) and NLRP3-/- THP-1 cells were exposed to SD at 50 µg/cm². Using a Vitrocell® Cloud, A549/THP-1 WT ALI co-cultures were exposed to SD or DQ12 quartz at non-cytotoxic concentrations of 10, 20, and 30 µg/cm². Additionally, ALI co-cultures containing NLRP3-/- or CASPASE1/- THP-1 cells were exposed to SD. SD was found to contain endotoxin, and caused manifold higher interleukin (IL)-1β secretion in WT than in NLRP3/- THP-1 cells. Baked SD (220°C, overnight) induced IL-1β secretion to a ~4-fold lower extent. Co-exposure to baked SD and endotoxin synergistically restored the IL-1β secretion. In ALI co-cultures SD but not DQ12 upregulated the expression and secretion of IL-1β, IL-6, IL-8, and tumor necrosis factor α. The secretion of these cytokines was strongly decreased in co-cultures with CASPASE1/- or NLRP3/- THP-1 cells. The screening of multiple SD samples on WT THP-1 cells revealed that their inflammatory potencies strongly depended on the sampling day and location. The surprisingly strong SD-mediated activation of the NLRP3 inflammasome emphasizes its hazardousness and the need for risk mitigation strategies. Therefore, the connection between the toxicity of SD and its composition, especially its microbial components, needs to be further unraveled. Supported by the Leibniz Collaborative Excellence Programme project DUSTRISK.

APA, Harvard, Vancouver, ISO, and other styles

17

D’Angelo, Davide, Eride Quarta, Stefania Glieca, Giada Varacca, Lisa Flammini, Simona Bertoni, Martina Brandolini, et al. "An Enhanced Dissolving Cyclosporin-A Inhalable Powder Efficiently Reduces SARS-CoV-2 Infection In Vitro." Pharmaceutics 15, no. 3 (March 22, 2023): 1023. http://dx.doi.org/10.3390/pharmaceutics15031023.

Full text

Abstract:

This work illustrates the development of a dry inhalation powder of cyclosporine-A for the prevention of rejection after lung transplantation and for the treatment of COVID-19. The influence of excipients on the spray-dried powder’s critical quality attributes was explored. The best-performing powder in terms of dissolution time and respirability was obtained starting from a concentration of ethanol of 45% (v/v) in the feedstock solution and 20% (w/w) of mannitol. This powder showed a faster dissolution profile (Weibull dissolution time of 59.5 min) than the poorly soluble raw material (169.0 min). The powder exhibited a fine particle fraction of 66.5% and an MMAD of 2.97 µm. The inhalable powder, when tested on A549 and THP-1, did not show cytotoxic effects up to a concentration of 10 µg/mL. Furthermore, the CsA inhalation powder showed efficiency in reducing IL-6 when tested on A549/THP-1 co-culture. A reduction in the replication of SARS-CoV-2 on Vero E6 cells was observed when the CsA powder was tested adopting the post-infection or simultaneous treatment. This formulation could represent a therapeutic strategy for the prevention of lung rejection, but is also a viable approach for the inhibition of SARS-CoV-2 replication and the COVID-19 pulmonary inflammatory process.

APA, Harvard, Vancouver, ISO, and other styles

18

Zhang, Xiaocheng, Mingyang Zhu, Zipu Hong, and Chengshui Chen. "Co-culturing polarized M2 Thp-1-derived macrophages enhance stemness of lung adenocarcinoma A549 cells." Annals of Translational Medicine 9, no. 8 (April 2021): 709. http://dx.doi.org/10.21037/atm-21-1256.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Nyiramana, Marie Merci, Soo Buem Cho, Eun-Jin Kim, Min Jun Kim, Ji Hyeon Ryu, Hyun Jae Nam, Nam-Gil Kim, et al. "Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways." Cancers 12, no. 3 (March 19, 2020): 726. http://dx.doi.org/10.3390/cancers12030726.

Full text

Abstract:

Sea hare-derived compounds induce macrophage activation and reduce asthmatic parameters in mouse models of allergic asthma. These findings led us to study the role of sea hare hydrolysates (SHH) in cancer pathophysiology. SHH treatment-induced M1 macrophage activation in RAW264.7 cells, peritoneal macrophages, and THP-1 cells, as did lipopolysaccharide (LPS) (+ INF-γ), whereas SHH reduced interleukin (IL)-4 (+IL-13)-induced M2 macrophage polarization. In addition, SHH treatment inhibited the actions of M1 and M2 macrophages, which have anticancer and pro-cancer effects, respectively, in non-small cell lung cancer cells (A549 and HCC-366) and tumor-associated macrophages (TAMs). Furthermore, SHH induced G2/M phase arrest and cell death in A549 cells. SHH also downregulated STAT3 activation in macrophages and A549 cells, and the down-regulation was recovered by colivelin, a STAT3 activator. SHH-induced reduction of M2 polarization and tumor growth was blocked by colivelin treatment. SHH-induced cell death did not occur in the manner of apoptotic signaling pathways, while the death pattern was mediated through pyroptosis/necroptosis, which causes membrane rupture, formation of vacuoles and bleb, activation of caspase-1, and secretion of IL-1β in SHH-treated A549 cells. However, a combination of SHH and colivelin blocked caspase-1 activation. Z-YVAD-FMK and necrostatin-1, pyrotosis and necroptosis inhibitors, attenuated SHH’s effect on the cell viability of A549 cells. Taken together, SHH showed anticancer effects through a cytotoxic effect on A549 cells and a regulatory effect on macrophages in A549 cells. In addition, the SHH-induced anticancer effects were mediated by non-apoptotic regulated cell death pathways under STAT3 inhibition. These results suggest that SHH may be offered as a potential remedy for cancer immunotherapy.

APA, Harvard, Vancouver, ISO, and other styles

20

Sievers, Justus Thomas Obiajulu, Anom Bowolaksono, and R. Tedjo Sasmono. "Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines." Asian Pacific Journal of Tropical Biomedicine 14, no. 5 (May 2024): 215–24. http://dx.doi.org/10.4103/apjtb.apjtb_35_24.

Full text

Abstract:

Objective: To characterize the infection patterns and growth characteristics of the Zika virus (ZIKV) strain JMB-185 from Indonesia in various mammalian cell lines. Methods: ZIKV was grown in human (A549, HEK293, HepG2, Huh7, Jurkat, and THP-1) and non-human mammalian (RAW264.7, Vero, and Vero76) cell lines. Viral replication kinetics were measured using plaque assay, while intra- and extracellular viral RNA concentrations were assessed using RT-PCR. Flow cytometry was used to quantify the infected cells and cell viability was measured using an MTT assay. The ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining assay. Results: This ZIKV strain preferentially infected the lung, kidney, and liver cell lines A549, HEK293, Huh7, Vero, and Vero76, but not the immune cells Jurkat, RAW264.7, and THP-1. By contrast, the ZIKV showed no sign of infection in HepG2 cells, while maintaining viral titer over 3 days post-infection, with no infection recorded in immunostaining, no increase in viral RNA, and no indication of cell deterioration. Conclusions: The Indonesian ZIKV strain has a similar infection profile as other strains, except for its poor infectivity on HepG2 cells. Information on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

APA, Harvard, Vancouver, ISO, and other styles

21

Yao, Yanfen, Hong Wang, Xueqin Xi, Wei Sun, Junke Ge, and Pibao Li. "miR-150 and SRPK1 regulate AKT3 expression to participate in LPS-induced inflammatory response." Innate Immunity 27, no. 4 (May 2021): 343–50. http://dx.doi.org/10.1177/17534259211018800.

Full text

Abstract:

miR-150 was found to target the 3′-untranslated regions of AKT3, and the AKT pathway was affected by SR protein kinase 1 (SRPK1). However, the expression and significance of miR-150, AKT3 and SRPK1 in acute lung injury (ALI) were not clear. Here, we found that the expression of miR-150 was significantly reduced, while the expression of AKT3 and SRPK1 were markedly increased in LPS-treated A549, THP-1 and RAW 264.7 cells. miR-150 significantly decreased levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, reduced the expression of AKT3, but had no impact on SRPK1 expression compared with the control group in LPS-treated A549, THP-1 and RAW 264.7 cells. AKT3 silencing only reduced the production of pro-inflammatory cytokines and showed no effect on miR-150 and SRPK1 expression. Finally, we observed that miR-150 mimics and/or silencing of SRPK1 decreased the expression of AKT3 mRNA. Besides, over-expression of miR-150 or silencing of SRPK1 also reduced the expression of AKT3 protein, which exhibited the lowest level in the miR-150 mimics plus si-SRPK1 group. However, si-SRPK1 had no effect on miR-150 level. In conclusion, miR-150 and SRPK1 separately and cooperatively participate into inflammatory responses in ALI through regulating AKT3 pathway. Increased miR-150 and silenced SRPK1 may be a novel potential factor for preventing and treating more inflammatory lung diseases.

APA, Harvard, Vancouver, ISO, and other styles

22

Marriott, Helen M., Kate A. Gascoyne, Ravi Gowda, Ian Geary, Martin J. H. Nicklin, Francesco Iannelli, Gianni Pozzi, et al. "Interleukin-1β Regulates CXCL8 Release and Influences Disease Outcome in Response to Streptococcus pneumoniae, Defining Intercellular Cooperation between Pulmonary Epithelial Cells and Macrophages." Infection and Immunity 80, no. 3 (December 12, 2011): 1140–49. http://dx.doi.org/10.1128/iai.05697-11.

Full text

Abstract:

The success ofStreptococcus pneumoniae(the pneumococcus) as a pulmonary pathogen is related to its restriction of innate immune responses by respiratory epithelial cells. The mechanisms used to overcome this restriction are incompletely elucidated. Pulmonary chemokine expression involves complex cellular and molecular networks, involving the pulmonary epithelium, but the specific cellular interactions and the cytokines that control them are incompletely defined. We show that serotype 2 or 4 pneumococci induce only modest levels of CXCL8 expression from epithelial cell lines, even in the absence of a polysaccharide capsule. In contrast, coculture of A549 cells with the macrophage-like THP-1 cell line, differentiated with vitamin D, or monocyte-derived macrophages enhanced CXCL8 release. Supernatants from the THP-1 cell line prime A549 cells to release CXCL8 at levels similar to cocultures. Interleukin-1Ra (IL-1Ra) inhibits CXCL8 release from cocultures and reduces the activity of macrophage-conditioned media, but inhibition of tumor necrosis factor alpha (TNF-α) had only a minimal effect on CXCL8 release. Release of IL-1β but not TNF-α was upregulated in cocultures. IL-1 type 1 receptor knockout C57BL/6 and BALB/c mice confirmed the importance of IL-1 signaling in CXC chemokine expression and neutrophil recruitmentin vivo. In fulminant disease, increased IL-1 signaling resulted in increased neutrophils in the airway and more invasive disease. These results demonstrate that IL-1 is an important component of the cellular network involving macrophages and epithelial cells, which facilitates CXC chemokine expression and aids neutrophil recruitment during pneumococcal pneumonia. They also highlight a potential clinical role for anti-IL-1 treatment to limit excessive neutrophilic inflammation in the lung.

APA, Harvard, Vancouver, ISO, and other styles

23

Carrillo-Romero, Juliana, Gartze Mentxaka, Adrián García-Salvador, Alberto Katsumiti, Susana Carregal-Romero, and Felipe Goñi-de-Cerio. "Assessing the Toxicity of Metal- and Carbon-Based Nanomaterials In Vitro: Impact on Respiratory, Intestinal, Skin, and Immune Cell Lines." International Journal of Molecular Sciences 25, no. 20 (October 10, 2024): 10910. http://dx.doi.org/10.3390/ijms252010910.

Full text

Abstract:

The field of nanotechnology has experienced exponential growth, with the unique properties of nanomaterials (NMs) being employed to enhance a wide range of products across diverse industrial sectors. This study examines the toxicity of metal- and carbon-based NMs, with a particular focus on titanium dioxide (TiO2), zinc oxide (ZnO), silica (SiO2), cerium oxide (CeO2), silver (Ag), and multi-walled carbon nanotubes (MWCNTs). The potential health risks associated with increased human exposure to these NMs and their effect on the respiratory, gastrointestinal, dermal, and immune systems were evaluated using in vitro assays. Physicochemical characterisation of the NMs was carried out, and in vitro assays were performed to assess the cytotoxicity, genotoxicity, reactive oxygen species (ROS) production, apoptosis/necrosis, and inflammation in cell lines representative of the systems evaluated (3T3, Caco-2, HepG2, A549, and THP-1 cell lines). The results obtained show that 3T3 and A549 cells exhibit high cytotoxicity and ROS production after exposure to ZnO NMs. Caco-2 and HepG2 cell lines show cytotoxicity when exposed to ZnO and Ag NMs and oxidative stress induced by SiO2 and MWCNTs. THP-1 cell line shows increased cytotoxicity and a pro-inflammatory response upon exposure to SiO2. This study emphasises the importance of conducting comprehensive toxicological assessments of NMs given their physicochemical interactions with biological systems. Therefore, it is of key importance to develop robust and specific methodologies for the assessment of their potential health risks.

APA, Harvard, Vancouver, ISO, and other styles

24

Arezki, Yasmin, Juliette Cornacchia, Mickaël Rapp, Luc Lebeau, Françoise Pons, and Carole Ronzani. "A Co-Culture Model of the Human Respiratory Tract to Discriminate the Toxicological Profile of Cationic Nanoparticles According to Their Surface Charge Density." Toxics 9, no. 9 (August 31, 2021): 210. http://dx.doi.org/10.3390/toxics9090210.

Full text

Abstract:

This study aimed at discriminating with sensitivity the toxicological effects of carbon dots (CDs) with various zeta potential (ζ) and charge density (Qek) in different cellular models of the human respiratory tract. One anionic and three cationic CDs were synthetized as follows: CD-COOH (ζ = −43.3 mV); CD-PEI600 (Qek = 4.70 µmol/mg; ζ = +31.8 mV); CD-PEHA (Qek = 3.30 µmol/mg; ζ = +29.2 mV) and CD-DMEDA (Qek = 0.01 µmol/mg; ζ = +11.1 mV). Epithelial cells (A549) and macrophages (THP-1) were seeded alone or as co-cultures with different A549:THP-1 ratios. The obtained models were characterized, and multiple biological responses evoked by CDs were assessed in the mono-cultures and the best co-culture model. With 14% macrophages, the 2:1 ratio co-culture best mimicked the in vivo conditions and responded to lipopolysaccharides. The anionic CD did not induce any effect in the mono-cultures nor in the co-culture. Among the cationic CDs, the one with the highest charge density (CD-PEI600) induced the most pronounced responses whatever the culture model. The cationic CDs of low charge density (CD-PEHA and CD-DMEDA) evoked similar responses in the mono-cultures, whereas in the co-culture, the three cationic CDs ranked according to their charge density (CD-PEI600 > CD-PEHA > CD-DMEDA), when taking into account their inflammatory effect. Thus, the co-culture system developed in this study appears to be a sensitive model for finely discriminating the toxicological profile of cationic nanoparticles differing by the density of their surface charges.

APA, Harvard, Vancouver, ISO, and other styles

25

Shimizu, Kaori, Shosaku Kashiwada, and Masanori Horie. "Cellular Effects of Silver Nanoparticle Suspensions on Lung Epithelial Cells and Macrophages." Applied Sciences 12, no. 7 (March 31, 2022): 3554. http://dx.doi.org/10.3390/app12073554.

Full text

Abstract:

Background: Silver nanoparticles (AgNPs) are used in industrial applications as catalysts, sanitary materials, and health supplements. Generally, AgNPs have shown cytotoxicity such as cell membrane damage. However, the mechanisms of their toxicity have not been completely elucidated. Methods: The cellular effects (cell viability, induction of chemokine and cellular oxidative stress) of two AgNP water suspensions (AgNP-A for cosmetic application and AgNP-B for industrial application) on epithelial-like A549 cells and macrophage-like differentiated THP-1 (dTHP-1) cells were examined. Results: AgNPs caused enhancement of IL-8 expression and oxidative stress. The cellular uptake of AgNP-A cells was observed. However, the cellular uptake of AgNP-B into A549 cells was hardly observed. Moreover, the intracellular Ag level was increased by AgNP suspensions exposure. Cell viability was not affected by AgNP suspensions exposure. Conclusions: AgNPs induce chemokine expression and cellular oxidative stress on culture cells. The intracellular Ag level may be important for these cellular effects.

APA, Harvard, Vancouver, ISO, and other styles

26

Cappellini, Francesca, Sebastiano Di Bucchianico, Venkatanaidu Karri, Siiri Latvala, Maria Malmlöf, Maria Kippler, Karine Elihn, et al. "Dry Generation of CeO2 Nanoparticles and Deposition onto a Co-Culture of A549 and THP-1 Cells in Air-Liquid Interface—Dosimetry Considerations and Comparison to Submerged Exposure." Nanomaterials 10, no. 4 (March 27, 2020): 618. http://dx.doi.org/10.3390/nano10040618.

Full text

Abstract:

Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is to expose lung cells under submerged conditions, but the cellular responses to NPs under such conditions might differ from those observed at the more physiological air-liquid interface (ALI). The aim of this study was to investigate the cytotoxic and inflammatory potential of CeO2 NPs (NM-212) in a co-culture of A549 lung epithelial cells and differentiated THP-1 cells in both ALI and submerged conditions. Cellular dose was examined quantitatively using inductively coupled plasma mass spectrometry (ICP-MS). The role of serum and LPS-priming for IL-1β release was further tested in THP-1 cells in submerged exposure. An aerosol of CeO2 NPs was generated by using the PreciseInhale® system, and NPs were deposited on the co-culture using XposeALI®. No or minor cytotoxicity and no increased release of inflammatory cytokines (IL-1β, IL-6, TNFα, MCP-1) were observed after exposure of the co-culture in ALI (max 5 µg/cm2) or submerged (max 22 µg/cm2) conditions. In contrast, CeO2 NPs cause clear IL-1β release in monocultures of macrophage-like THP-1, independent of the presence of serum and LPS-priming. This study demonstrates a useful approach for comparing effects at various in-vitro conditions.

APA, Harvard, Vancouver, ISO, and other styles

27

Zbakh, Hanaa, Eva Zubía, Carolina de los Reyes, José M. Calderón-Montaño, Miguel López-Lázaro, and Virginia Motilva. "Meroterpenoids from the Brown Alga Cystoseira usneoides as Potential Anti-Inflammatory and Lung Anticancer Agents." Marine Drugs 18, no. 4 (April 11, 2020): 207. http://dx.doi.org/10.3390/md18040207.

Full text

Abstract:

The anti-inflammatory and anticancer properties of eight meroterpenoids isolated from the brown seaweed Cystoseira usneoides have been evaluated. The algal meroterpenoids (AMTs) 1–8 were tested for their inhibitory effects on the production of the pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and the expression of cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in LPS-stimulated THP-1 human macrophages. The anticancer effects were assessed by cytotoxicity assays against human lung adenocarcinoma A549 cells and normal lung fibroblastic MRC-5 cells, together with flow cytometry analysis of the effects of these AMTs on different phases of the cell cycle. The AMTs 1–8 significantly reduced the production of TNF-α, IL-6, and IL-1β, and suppressed the COX-2 and iNOS expression, in LPS-stimulated cells (p < 0.05). The AMTs 1–8 displayed higher cytotoxic activities against A549 cancer cells than against MRC-5 normal lung cells. Cell cycle analyses indicated that most of the AMTs caused the arrest of A549 cells at the G2/M and S phases. The AMTs 2 and 5 stand out by combining significant anti-inflammatory and anticancer activities, while 3 and 4 showed interesting selective anticancer effects. These findings suggest that the AMTs produced by C. usneoides may have therapeutic potential in inflammatory diseases and lung cancer.

APA, Harvard, Vancouver, ISO, and other styles

28

Roth, Amelie, Astrid Tannert, Nadja Ziller, Simone Eiserloh, Bianca Göhrig, Rustam R. Guliev, María José Gonzalez Vazquez, et al. "Quantification of Polystyrene Uptake by Different Cell Lines Using Fluorescence Microscopy and Label-Free Visualization of Intracellular Polystyrene Particles by Raman Microspectroscopic Imaging." Cells 13, no. 5 (March 5, 2024): 454. http://dx.doi.org/10.3390/cells13050454.

Full text

Abstract:

Environmental pollution caused by plastic is a present problem. Polystyrene is a widely used packaging material (e.g., Styrofoam) that can be broken down into microplastics through abrasion. Once the plastic is released into the environment, it is dispersed by wind and atmospheric dust. In this study, we investigated the uptake of polystyrene particles into human cells using A549 cells as a model of the alveolar epithelial barrier, CaCo-2 cells as a model of the intestinal epithelial barrier, and THP-1 cells as a model of immune cells to simulate a possible uptake of microplastics by inhalation, oral uptake, and interaction with the cellular immune system, respectively. The uptake of fluorescence-labeled beads by the different cell types was investigated by confocal laser scanning microscopy in a semi-quantitative, concentration-dependent manner. Additionally, we used Raman spectroscopy as a complementary method for label-free qualitative detection and the visualization of polystyrene within cells. The uptake of polystyrene beads by all investigated cell types was detected, while the uptake behavior of professional phagocytes (THP-1) differed from that of adherent epithelial cells.

APA, Harvard, Vancouver, ISO, and other styles

29

Sarwar, Saira, Rebecca Aicheler, Lee Butcher, Katie Rees, Stephen Potter, Richard Rowlands, and Richard Webb. "The rs2228145 Variant of the Interleukin-6 Receptor (IL-6R) Gene Impacts on In Vitro Cellular Responses to SARS-CoV-2 VOC B1.1.7 Recombinant Spike Protein." COVID 3, no. 10 (October 3, 2023): 1554–70. http://dx.doi.org/10.3390/covid3100106.

Full text

Abstract:

Given the variability in inflammatory responses to SARS-CoV-2 infection observed within human populations, we aimed to develop an in vitro model system (based on monocyte-macrophages, a key relevant cell type) that could yield insights regarding the impact of rs2228145, a clinically relevant polymorphism within the coding region of a key inflammatory gene in the body’s response to SARS-CoV-2 infection: the interleukin-6 receptor (IL-6R) gene. Three monocyte-macrophage cell-lines (U937, THP-1, MM6) were shown to exhibit AA, AC and CC rs2228145 genotypes, respectively, and to exhibit an MM6 > THP-1 > U937 pattern regarding basal levels of soluble IL-6R (sIL-6R) release. Similar MM6 > THP-1 > U937 patterns were seen regarding the extents to which (i) circulating levels of the IL-6/sIL-6R ‘active complex’ increased and (ii) phosphorylation of the downstream transcription-factor STAT3 occurred, following treatment with SARS-CoV-2 spike protein (SP). Moreover, a blocking antibody for the ACE-2 entry receptor for SARS-CoV-2 suppressed effects (i) and (ii), suggesting that interaction between SP and ACE-2 is the initial event that triggers IL-6/IL-6R signalling in our system. Production of IL-8 occurred to greater extents in A549 lung epithelial cells treated with tissue-culture supernatants from SP-treated MM6 cultures than SP-treated THP-1 or U937 cultures. Our data indicate that the rs2228145 genotype significantly impacts upon SP-associated IL-6/sIL-6R signalling in vitro, suggesting that it may influence in vivo risk of developing severe COVID-19 and/or long-COVID symptoms following infection by SARS-CoV-2. Thus, the rs2228145 genotype may have potential as a biomarker that differentiates between patients at risk of developing severe and/or prolonged symptoms following infection by SARS-CoV-2 and those who are at less risk.

APA, Harvard, Vancouver, ISO, and other styles

30

Nahid, Md A., Minoru Satoh, and Edward K. L. Chan. "Interleukin 1β-Responsive MicroRNA-146a Is Critical for the Cytokine-Induced Tolerance and Cross-Tolerance to Toll-Like Receptor Ligands." Journal of Innate Immunity 7, no. 4 (2015): 428–40. http://dx.doi.org/10.1159/000371517.

Full text

Abstract:

Unwarranted overproduction of cytokines, such as interleukin (IL)-1β, can cause moderate to severe pathological complications, and thus elaborate mechanisms are needed to regulate its onset and termination. One such, well-known, mechanism is endotoxin tolerance, generally described as controlling lipopolysaccharide Toll-like receptor 4 (LPS-TLR4) signaling. Similarly, cytokine-induced tolerance plays an important role in regulating an overactive cytokine response. In this report, the capability of IL-1β to induce tolerance and cross-tolerance to various inflammatory ligands was investigated. IL-1β-stimulated THP-1 monocytes showed a gradual increase of microRNA (miR)-146a, reaching 15-fold expression by 24 h. miR-146a upregulation induced tolerance toward subsequent challenges of IL-1β, LPS, peptidoglycan, Pam and flagellin in THP-1 cells. The induction of tolerance was dependent on the IL-1β priming dose and associated increase of miR-146a expression. Moreover, IL-1β-treated THP-1 cells showed sustained miR-146a upregulation that repressed IRAK1 and TRAF6 adaptor molecules. Transfection of miR-146a alone mimicked IL-1β-induced tolerance in monocytes, while cells transfected with miR-146a inhibitor increased chemokine production. A comparable cytokine response regulated by miR-146a was also detected in lung epithelial A549 cells, purified human monocytes and mouse peritoneal macrophages. Thus, our studies showed that miR-146a was crucial for monocytic cell-based IL-1β tolerance and cross-tolerance, and thus opens the way for future research in the development of therapeutics for inflammatory diseases.

APA, Harvard, Vancouver, ISO, and other styles

31

Oh, Suyeon, and Young-Hee Kang. "Aesculetin Attenuates Pulmonary Fibrosis Induced by Close Contact of Macrophages with Alveolar Epithelial Cells." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1531. http://dx.doi.org/10.1093/cdn/nzaa068_016.

Full text

Abstract:

Abstract Objectives Pulmonary fibrosis is a disease in which lung tissues become fibrous and causes severe respiratory disturbances. Various stimuli induce infiltration of macrophages to the respiratory tract. These macrophages secrete various inflammatory cytokines leading to development of pulmonary fibrosis via epithelial–mesenchymal transition (EMT) process. Aesculetin, a major component of Sancho tree and Chicory, is known to have antioxidant and anti-inflammatory effects in the vascular and immune system. Methods Human alveolar basal epithelial A549 cells were cultured in conditioned media of THP-1 monocyte-derived macrophages for 24 h. Aesculetin at the concentrations of 1–20 μM did not show cytotoxicity of A549 cells. Alveolar epithelial cells were incubated with interleukin (IL)-8. Western blotting examined EMT-associated fibrotic proteins from A549 cell lysates. Matrix metalloproteinase (MMP) activity was measured with gelatin zymography. In addition, inflammation- and fibrosis-related cytokines were measured by using ELISA kits. Results The epithelial markers of E-cadherin and ZO-1 were reduced in cells exposed to macrophage-conditioned media containing IL-8 and TNF-α. Macrophage-conditioned media enhanced expression of the mesenchymal fibrotic markers of α-smooth muscle actin (α-SMA), vimentin and fibronectin, and the fibrotic proteins of collagen I and collagen IV were enhanced. However, ≥10 μM aesculetin reciprocally manipulated the expression levels of these proteins of A549 cells. In addition, macrophage-conditioned media enhanced the expression and activity of MT1-MMP, MMP-2 and MMP-9. In contrast, the expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 were reduced by exposure of alveolar cells to conditioned media. Proinflammatory and chemotactic IL-8 reduced E-cadherin and conversely enhanced N-cadherin and α-SMA in A549 cells, which was reciprocally modulated by ≥ 10 μM aesculetin. These results demonstrate that aesculetin may ameliorate EMT-associated pulmonary fibrosis caused by contact of blood-derived macrophages and alveolar cells. Conclusions Aesculetin maybe a promising agent treating progressive pulmonary disorders owing to macrophage-mediated inflammation. Funding Sources No funding sources to report.

APA, Harvard, Vancouver, ISO, and other styles

32

Florio, Walter, Franca Lisa Brancatisano, Daria Bottai, Semih Esin, Mariagrazia Di Luca, Claudio Counoupas, Giuseppantonio Maisetta, Antonella Lupetti, Giovanna Batoni, and Mario Campa. "TheBCG1619cgene is not essential for invasion and intracellular persistence ofMycobacterium bovisBCG in human THP-1 and A549 cell lines." Canadian Journal of Microbiology 55, no. 8 (August 2009): 975–82. http://dx.doi.org/10.1139/w09-053.

Full text

Abstract:

The BCG1619c gene of Mycobacterium bovis bacillus Calmette–Guérin (BCG) encodes for a 24 kDa invasin-like protein and is identical to the Rv1566c gene of Mycobacterium tuberculosis . To assess whether this protein was necessary for entry and (or) intracellular persistence in professional phagocytes and (or) in lung epithelial cells, a BCG1619c knockout mutant of M. bovis BCG was generated and compared with the parental BCG strain for its ability to infect and multiply in human monocyte derived THP-1 cells and in the lung epithelial cell line A549. No significant difference between the mutated and the parental BCG strain was observed in either of these in vitro infection systems, indicating that the BCG1619c gene is not essential for cell invasion and intracellular growth of BCG.

APA, Harvard, Vancouver, ISO, and other styles

33

Thiruvenkataramani, Ranga P., Amal Abdul-Hafez, Tulasi Kesaraju, Hend Mohamed, Sherif Abdelfattah Ibrahim, Amira Othman, Hattan Arif, et al. "Small Extracellular Vesicles Derived from Cord Blood Plasma and Placental Mesenchymal Stem Cells Attenuate Acute Lung Injury Induced by Lipopolysaccharide (LPS)." International Journal of Molecular Sciences 26, no. 1 (December 25, 2024): 75. https://doi.org/10.3390/ijms26010075.

Full text

Abstract:

Sepsis is a risk factor associated with increasing neonatal morbidity and mortality, acute lung injury, and chronic lung disease. While stem cell therapy has shown promise in alleviating acute lung injury, its effects are primarily exerted through paracrine mechanisms rather than local engraftment. Accumulating evidence suggests that these paracrine effects are mediated by mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs), which play a critical role in immune system modulation and tissue regeneration. sEVs contain a diverse cargo of mRNA, miRNA, and proteins, contributing to their therapeutic potential. We hypothesize that sEVs derived from three distinct sources, cord blood plasma (CBP), Wharton jelly (WJ), and placental (PL) MSCs, may prevent the cytotoxicity induced by E. coli lipopolysaccharide (LPS) in lung alveolar epithelial cells. Objective: To determine the effects of CBP-, WJ-, and PL-MSCs-derived sEVs on cell viability, apoptosis, and proinflammatory cytokine production in alveolar epithelial cells and monocytes following LPS treatment. sEVs were collected from conditioned media of PL-MSCs, WJ-MSCs, and CBP using 50 nm membrane filters. sEVs were characterized based on nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting techniques. The protein concentration of isolated sEVs was used to standardize treatment doses. A549 cells and monocyte THP-1 cells were cultured and exposed to LPS in the presence or absence of sEVs for 72 h. Cell viability was measured using CellTiter-Glo 2.0 chemiluminescence-based assay. For cytokine analysis, A549 and THP-1 cells were pre-incubated for 24 h with or without PL- and CBP-sEVs, followed by exposure to LPS or control conditions for an additional 24 h. The conditioned media were collected, and interleukin-6 (IL-6) and interleukin-8 (IL-8) levels were quantified using ELISA. LPS treatment significantly reduced the viability of both A549 and THP-1 cells. The presence of CB- or WJ-sEVs significantly increased cell viability compared to controls. Cells treated with PL-sEVs showed increased cell viability but did not reach statistical significance. LPS-treated cells showed a significant increase in apoptosis and elevated levels of pro-inflammatory cytokines IL-6 and IL-8. All three sEVs types (CBP-, WJ-, and PL-sEVs) significantly reduced LPS-induced apoptosis and IL-6 release. Interestingly, while WJ-sEVs decreased IL-8, both CBP- and PL-sEVs led to an increase in IL-8 compared to their respective controls. CBP-, PL-, and WJ-derived sEVs demonstrated protective effects against LPS-induced injury in alveolar epithelial cells and monocytes, as evidenced by increased cell viability and modulation of pro-inflammatory cytokine release. These findings suggest that placenta-derived sEVs have the potential to modulate the immune response, mitigate inflammation, and prevent end-organ damage in neonatal sepsis.

APA, Harvard, Vancouver, ISO, and other styles

34

Meindl, Claudia, Markus Absenger-Novak, Ramona Jeitler, Eva Roblegg, and Eleonore Fröhlich. "Assessment of Carbon Nanotubes on Barrier Function, Ciliary Beating Frequency and Cytokine Release in In Vitro Models of the Respiratory Tract." Nanomaterials 13, no. 4 (February 9, 2023): 682. http://dx.doi.org/10.3390/nano13040682.

Full text

Abstract:

The exposure to inhaled carbon nanotubes (CNT) may have adverse effects on workers upon chronic exposure. In order to assess the toxicity of inhaled nanoparticles in a physiologically relevant manner, an air–liquid interface culture of mono and cocultures of respiratory cells and assessment in reconstructed bronchial and alveolar tissues was used. The effect of CNT4003 reference particles applied in simulated lung fluid was studied in bronchial (Calu-3 cells, EpiAirway™ and MucilAir™ tissues) and alveolar (A549 +/−THP-1 and EpiAlveolar™ +/−THP-1) models. Cytotoxicity, transepithelial electrical resistance, interleukin 6 and 8 secretion, mucociliary clearance and ciliary beating frequency were used as readout parameters. With the exception of increased secretion of interleukin 6 in the EpiAlveolar™ tissues, no adverse effects of CNT4003 particles, applied at doses corresponding to the maximum estimated lifetime exposure of workers, in the bronchial and alveolar models were noted, suggesting no marked differences between the models. Since the doses for whole-life exposure were applied over a shorter time, it is not clear if the interleukin 6 increase in the EpiAlveolar™ tissues has physiological relevance.

APA, Harvard, Vancouver, ISO, and other styles

35

Yanamala, Naveena, Elena R. Kisin, Autumn L. Menas, Mariana T. Farcas, Timur O. Khaliullin, Ulla B. Vogel, Galina V. Shurin, et al. "In Vitro Toxicity Evaluation of Lignin-(Un)coated Cellulose Based Nanomaterials on Human A549 and THP-1 Cells." Biomacromolecules 17, no. 11 (October 21, 2016): 3464–73. http://dx.doi.org/10.1021/acs.biomac.6b00756.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Sueki, Akane, Kazuyuki Matsuda, Chinami Iwashita, Chiaki Taira, Nau Ishimine, Shohei Shigeto, Kenji Kawasaki, Mitsutoshi Sugano, Hiroshi Yamamoto, and Takayuki Honda. "Epithelial–mesenchymal transition of A549 cells is enhanced by co-cultured with THP-1 macrophages under hypoxic conditions." Biochemical and Biophysical Research Communications 453, no. 4 (October 2014): 804–9. http://dx.doi.org/10.1016/j.bbrc.2014.10.022.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Furukawa, Satomi, Kazuyuki Matsuda, Mitsutoshi Sugano, Takeshi Uehara, and Takayuki Honda. "NLRP3 upregulation in A549 cells co-cultured with THP-1 macrophages under hypoxia via deregulated TGF-β signaling." Experimental Cell Research 383, no. 1 (October 2019): 111506. http://dx.doi.org/10.1016/j.yexcr.2019.111506.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Kim, Young Hun, Hyeoung Woo Park, Zae Young Ryoo, Hyun-Shik Lee, Do-Hyung Kim, and Sanggyu Lee. "Abnormal effects of unpurified and purified multi-walled carbon nanotubes in A549, Jurkat and THP-1 cell lines." Molecular & Cellular Toxicology 8, no. 1 (March 2012): 103–12. http://dx.doi.org/10.1007/s13273-012-0013-9.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Wood, Rebecca E., Patrice Newton, Eleanor A. Latomanski, and Hayley J. Newton. "Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires." Infection and Immunity 83, no. 10 (July 27, 2015): 4081–92. http://dx.doi.org/10.1128/iai.00461-15.

Full text

Abstract:

Legionellaorganisms are environmental bacteria and accidental human pathogens that can cause severe pneumonia, termed Legionnaires' disease. These bacteria replicate within a pathogen-derived vacuole termed theLegionella-containing vacuole (LCV). Our understanding of the development and dynamics of this vacuole is based on extensive analysis ofLegionella pneumophila. Here, we have characterized theLegionella longbeachaereplicative vacuole (longbeachae-LCV) and demonstrated that, despite important genomic differences, key features of the replicative LCV are comparable to those of the LCV ofL. pneumophila(pneumophila-LCV). We constructed a Dot/Icm-deficient strain by deletingdotBand demonstrated the inability of this mutant to replicate inside THP-1 cells.L. longbeachaedoes not enter THP-1 cells as efficiently asL. pneumophila, and this is reflected in the observation that translocation of BlaM-RalFLLO(where RalFLLOis theL. longbeachaehomologue of RalF) into THP-1 cells by theL. longbeachaeDot/Icm system is less efficient than that byL. pneumophila. This difference is negated in A549 cells whereL. longbeachaeandL. pneumophilainfect with similar entry dynamics. A β-lactamase assay was employed to demonstrate the translocation of a novel family of proteins, theRab-likeeffector (Rle) proteins. Immunofluorescence analysis confirmed that these proteins enter the host cell during infection and display distinct subcellular localizations, with RleA and RleC present on thelongbeachae-LCV. We observed that the host Rab GTPase, Rab1, and the v-SNARE Sec22b are also recruited to thelongbeachae-LCV during the early stages of infection, coinciding with the LCV avoiding endocytic maturation. These studies further our understanding of theL. longbeachaereplicative vacuole, highlighting phenotypic similarities to the vacuole ofL. pneumophilaas well as unique aspects of LCV biology.

APA, Harvard, Vancouver, ISO, and other styles

40

Wardhani, Kartika, Aviva Levina, Biyun Sun, Haipei Zou, Georges E. R. Grau, F. Richard Keene, J. Grant Collins, and Peter A. Lay. "Tetranuclear Polypyridylruthenium(II) Complexes as Selective Nucleic Acid Stains for Flow Cytometric Analysis of Monocytic and Epithelial Lung Carcinoma Large Extracellular Vesicles." Biomolecules 14, no. 6 (June 6, 2024): 664. http://dx.doi.org/10.3390/biom14060664.

Full text

Abstract:

Selective staining of extracellular vesicles (EVs) is a major challenge for diagnostic and therapeutic applications. Herein, the EV labeling properties of a new class of tetranuclear polypyridylruthenium(II) complexes, Rubb7-TNL and Rubb7-TL, as phosphorescent stains are described. These new stains have many advantages over standard stains to detect and characterize EVs, including: high specificity for EV staining versus cell staining; high phosphorescence yields; photostability; and a lack of leaching from EVs until incorporation with target cells. As an example of their utility, large EVs released from control (basal) or lipopolysaccharide (LPS)-stimulated THP-1 monocytic leukemia cells were studied as a model of immune system EVs released during bacterial infection. Key findings from EV staining combined with flow cytometry were as follows: (i) LPS-stimulated THP-1 cells generated significantly larger and more numerous large EVs, as compared with those from unstimulated cells; (ii) EVs retained native EV physical properties after staining; and (iii) the new stains selectively differentiated intact large EVs from artificial liposomes, which are models of cell membrane fragments or other lipid-containing debris, as well as distinguished two distinct subpopulations of monocytic EVs within the same experiment, as a result of biochemical differences between unstimulated and LPS-stimulated monocytes. Comparatively, the staining patterns of A549 epithelial lung carcinoma-derived EVs closely resembled those of THP-1 cell line-derived EVs, which highlighted similarities in their selective staining despite their distinct cellular origins. This is consistent with the hypothesis that these new phosphorescent stains target RNA within the EVs.

APA, Harvard, Vancouver, ISO, and other styles

41

Kim, Mi-Jeong, Yoon Min, Juhee Son, Ji Young Kim, Ji Su Lee, Duk-Hwan Kim, and Ki-Young Lee. "AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis." Cancers 12, no. 11 (November 6, 2020): 3289. http://dx.doi.org/10.3390/cancers12113289.

Full text

Abstract:

TRAF6-BECN1 signaling axis is critical for autophagy induction and functionally implicated in cancer progression. Here, we report that AMP-activated protein kinase alpha 1 (AMPKα1, PRKAA1) is positively involved in autophagy induction and cancer progression by regulating TRAF6-BECN1 signaling axis. Mechanistically, AMPKα1 interacted with TRAF6 and BECN1. It also enhanced ubiquitination of BECN1 and autophagy induction. AMPKα1-knockout (AMPKα1KO) HEK293T or AMPKα1-knockdown (AMPKα1KD) THP-1 cells showed impaired autophagy induced by serum starvation or TLR4 (Toll-like receptor 4) stimulation. Additionally, AMPKα1KD THP-1 cells showed decreases of autophagy-related and autophagosome-related genes induced by TLR4. AMPKα1KO A549 cells exhibited attenuation of cancer migration and invasion induced by TLR4. Moreover, primary non-small cell lung cancers (NSCLCs, n = 6) with low AMPKαl levels showed markedly decreased expression of genes related to autophagy, cell migration and adhesion/metastasis, inflammation, and TLRs whereas these genes were significantly upregulated in NSCLCs (n = 5) with high AMPKαl levels. Consistently, attenuation of cancer migration and invasion could be observed in AMPKα1KO MDA-MB-231 and AMPKα1KO MCF-7 human breast cancer cells. These results suggest that AMPKα1 plays a pivotal role in cancer progression by regulating the TRAF6-BECN1 signaling axis for autophagy induction.

APA, Harvard, Vancouver, ISO, and other styles

42

Oh, Su Yeon, Yun-Ho Kim, Min-Kyung Kang, Eun-Jung Lee, Dong Yeon Kim, Hyeongjoo Oh, Soo-Il Kim, Woojin Na, and Young-Hee Kang. "Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling." International Journal of Molecular Sciences 21, no. 15 (August 1, 2020): 5518. http://dx.doi.org/10.3390/ijms21155518.

Full text

Abstract:

Pulmonary fibrosis is a disease in which lung tissues become fibrous and thereby causes severe respiratory disturbances. Various stimuli induce infiltration of macrophages to the respiratory tract, secreting inflammatory cytokines, which subsequently leads to the development of pulmonary fibrosis. Aesculetin, a major component of the sancho tree and chicory, is known to biologically have antioxidant and anti-inflammatory effects. Human alveolar epithelial A549 cells were cultured for 24 h in conditioned media of THP-1 monocyte-derived macrophages (mCM) with 1–20 μM aesculetin. Micromolar aesculetin attenuated the cytotoxicity of mCM containing inflammatory tumor necrosis factor-α (TNF)-α and interleukin (IL)-8 as major cytokines. Aesculetin inhibited alveolar epithelial induction of the mesenchymal markers in mCM-exposed/IL-8-loaded A549 cells (≈47–51% inhibition), while epithelial markers were induced in aesculetin-treated cells subject to mCM/IL-8 (≈1.5–2.3-fold induction). Aesculetin added to mCM-stimulated A549 cells abrogated the collagen production and alveolar epithelial CXC-chemokine receptor 2 (CXCR2) induction. The production of matrix metalloproteinase (MMP) proteins in mCM-loaded A549 cells was reduced by aesculetin (≈52% reduction), in parallel with its increase in tissue inhibitor of metalloproteinases (TIMP) proteins (≈1.8-fold increase). In addition, aesculetin enhanced epithelial induction of tight junction proteins in mCM-/IL-8-exposed cells (≈2.3–2.5-fold induction). The inhalation of polyhexamethylene guanidine (PHMG) in mice accompanied neutrophil predominance in bronchoalveolar lavage fluid (BALF) and macrophage infiltration in alveoli, which was inhibited by orally administrating aesculetin to mice. Treating aesculetin to mice alleviated PHMG-induced IL-8-mediated subepithelial fibrosis and airway barrier disruption. Taken together, aesculetin may antagonize pulmonary fibrosis and alveolar epithelial barrier disruption stimulated by the infiltration of monocyte-derived macrophages, which is typical of PHMG toxicity, involving interaction of IL-8 and CXCR2. Aesculetin maybe a promising agent counteracting macrophage-mediated inflammation-associated pulmonary disorders.

APA, Harvard, Vancouver, ISO, and other styles

43

Wong, Si Nga, Jingwen Weng, Ignatius Ip, Ruipeng Chen, Richard Lakerveld, Richard Telford, Nicholas Blagden, Ian J. Scowen, and Shing Fung Chow. "Rational Development of a Carrier-Free Dry Powder Inhalation Formulation for Respiratory Viral Infections via Quality by Design: A Drug-Drug Cocrystal of Favipiravir and Theophylline." Pharmaceutics 14, no. 2 (January 27, 2022): 300. http://dx.doi.org/10.3390/pharmaceutics14020300.

Full text

Abstract:

Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality-by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing a 1:1 favipiravir–theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy for individuals with concomitant influenza infections and chronic obstructive pulmonary disease/asthma. The cocrystal formation was confirmed by single crystal X-ray diffraction, powder X-ray diffraction, and the construction of a temperature–composition phase diagram. A three-factor, two-level, full factorial design was employed to produce the optimized formulation and study the impact of critical processing parameters on the resulting median mass aerodynamic diameter (MMAD), fine particle fraction (FPF), and crystallinity of the spray-dried FAV-THP cocrystal. In general, a lower solute concentration and feed pump rate resulted in a smaller MMAD with a higher FPF. The optimized formulation (F1) demonstrated an MMAD of 2.93 μm and an FPF of 79.3%, suitable for deep lung delivery with no in vitro cytotoxicity observed in A549 cells.

APA, Harvard, Vancouver, ISO, and other styles

44

Hoang, Thi Xoan, Cao Nguyen Duong, and Jae Young Kim. "Identification and Characterization of a Splicing Variant in the 5′ UTR of the Human TLR5 Gene." BioMed Research International 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/8727434.

Full text

Abstract:

Toll-like receptors (TLRs) are essential components of the innate immune system. TLR5 is the receptor for flagellin, the principal protein component of bacterial flagella. The TLR5 gene has 6 exons. In an RT-PCR analysis, we found long TLR5 transcripts, in addition to those of the expected size (short TLR5 transcripts). A sequence analysis revealed that the long TLR5 transcripts contain a new exon of 94 nucleotides located between previously reported exons IV and V in the 5′ untranslated region (5′ UTR). A real-time PCR analysis of the two alternatively spliced variants in various cell lines showed that the long TLR5 transcripts are abundantly expressed in nonimmune cells. The ratios of long/short transcripts in human nonimmune cell lines, such as A549, T98G, HaCaT, H460, HEK-293, and Caco-2 cells, and primary mesenchymal stem cells were in the range of 1.25 to 4.31. In contrast, those of human monocytic THP-1 and U937 cells and E6.1 T cells and Ramos B cells were around 0.9. These ratios in human monocytic THP-1 cells were decreased by treatment with IFN-γ in a concentration-dependent manner. Based on our findings, we suggest that the newly found long TLR5 transcripts may be involved in the negative regulation of TLR5 expression and function.

APA, Harvard, Vancouver, ISO, and other styles

45

Semmarath, Warathit, Sariya Mapoung, Sonthaya Umsumarng, Punnida Arjsri, Kamonwan Srisawad, Pilaiporn Thippraphan, Supachai Yodkeeree, and Pornngarm Dejkriengkraikul. "Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway." Nutrients 14, no. 13 (June 30, 2022): 2738. http://dx.doi.org/10.3390/nu14132738.

Full text

Abstract:

Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G and P3G-rich fraction of black rice germ and bran (BR extract) on the inhibition of inflammatory responses induced by SP, as well as the inhibition of NF-kB activation and the NLRP3 inflammasome pathway in an in vitro model. In this study, BR extract was identified for its active anthocyanins, C3G and P3G, using the HPLC technique. A549-lung cells and differentiated THP-1 macrophages were treated with BR extract, C3G, or P3G prior to exposure to 100 ng/mL of SP. Their anti-inflammatory properties were then determined. BR extract at concentrations of 12.5–100 μg/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1β, and IL-18 inflammatory gene expressions and IL-6, IL-1β, and IL-18 cytokine secretions in a dose-dependent manner (p < 0.05). It was determined that both cell lines, C3G and P3G (at 1.25–10 μg/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p < 0.05). With regard to the anti-inflammation mechanism, BR extract, C3G, and P3G could attenuate SP-induced inflammation via counteraction with NF-kB activation and downregulation of the inflammasome-dependent inflammatory pathway proteins (NLRP3, ASC, and capase-1). Overall, the protective effects of anthocyanins obtained from black rice germ and bran can be employed in potentially preventive strategies that use pigmented rice against the long-term sequelae of COVID-19 infection.

APA, Harvard, Vancouver, ISO, and other styles

46

Gupta, Pramod Kumar, Devavrat Tripathi, Savita Kulkarni, and M. G. R. Rajan. "Mycobacterium tuberculosis H37Rv infected THP-1 cells induce epithelial mesenchymal transition (EMT) in lung adenocarcinoma epithelial cell line (A549)." Cellular Immunology 300 (February 2016): 33–40. http://dx.doi.org/10.1016/j.cellimm.2015.11.007.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Gottipati, Koteswara R., Shiva Kumar Bandari, Matthew W. Nonnenmann, Jeffrey L. Levin, Gregory P. Dooley, Stephen J. Reynolds, and Vijay Boggaram. "Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 308, no. 1 (January 1, 2015): L11—L21. http://dx.doi.org/10.1152/ajplung.00215.2014.

Full text

Abstract:

Exposure to the agricultural work environment is a risk factor for the development of respiratory symptoms and chronic lung diseases. Inflammation is an important contributor to the pathogenesis of tissue injury and disease. Cellular and molecular mechanisms mediating lung inflammatory responses to agricultural dust are not yet fully understood. We studied the effects of poultry dust extract on molecular regulation of interleukin-8 (IL-8), a proinflammatory cytokine, in A549 and Beas2B lung epithelial and THP-1 monocytic cells. Our findings indicate that poultry dust extract potently induces IL-8 levels by increasing IL-8 gene transcription without altering IL-8 mRNA stability. Increase in IL-8 promoter activity was due to enhanced binding of activator protein 1 and NF-κB. IL-8 induction was associated with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activation and inhibited by PKC and MAPK inhibitors. IL-8 increase was not inhibited by polymyxin B or l-nitroarginine methyl ester, indicating lack of involvement of lipopolysaccharide and nitric oxide in the induction. Lung epithelial and THP-1 cells share common mechanisms for induction of IL-8 levels. Our findings identify key roles for transcriptional mechanisms and protein kinase signaling pathways for IL-8 induction and provide insights into the mechanisms regulating lung inflammatory responses to organic dust exposure.

APA, Harvard, Vancouver, ISO, and other styles

48

SB, Patil. "Anticancer Potential of Novel Pyrimidine Analogs: Recent Updates." Medicinal and Analytical Chemistry International Journal 8, no. 1 (January 31, 2024): 1–6. http://dx.doi.org/10.23880/macij-16000189.

Full text

Abstract:

Pyrimidine, having two nitrogen atoms, looks like pyridine and benzene. In nature, pyrimidine is present in different forms, such as the bases of DNA and RNA. Due to its structure, various kinds of biological activity have been observed. The substituted and fused pyrimidine derivatives were chemically synthesized and showed anti-cancer potential against cancer cell lines (SW480, A549, CCRF-CEM, THP-1, HepG2, HCT-116, PC3, Huh-7, CNE-2, MGC-803, and MDA-MB-435). Based on the experimental results, the substituted pyrimidines and fused derivatives showed remarkably enhanced anticancer activity, which may be due to the presence of Cl, F, Br, CH3O, aryl urea, indolyl pyrimidine, thienopyrimidine, benzyl amino pyrimidine and the pyrimidine moiety. In this article, recent anticancer research findings were highlighted

APA, Harvard, Vancouver, ISO, and other styles

49

Ventura, Célia, Fátima Pinto, Ana Filipa Lourenço, Jorge F. S. Pedrosa, Susete N. Fernandes, Rafaela R. da Rosa, Maria Helena Godinho, Paulo J. T. Ferreira, Henriqueta Louro, and Maria João Silva. "Assessing the Genotoxicity of Cellulose Nanomaterials in a Co-Culture of Human Lung Epithelial Cells and Monocyte-Derived Macrophages." Bioengineering 10, no. 8 (August 21, 2023): 986. http://dx.doi.org/10.3390/bioengineering10080986.

Full text

Abstract:

Cellulose micro/nanomaterials (CMNMs) are innovative materials with a wide spectrum of industrial and biomedical applications. Although cellulose has been recognized as a safe material, the unique properties of its nanosized forms have raised concerns about their safety for human health. Genotoxicity is an endpoint that must be assessed to ensure that no carcinogenic risks are associated with exposure to nanomaterials. In this study, we evaluated the genotoxicity of two types of cellulose micro/nanofibrils (CMF and CNF) and one sample of cellulose nanocrystals (CNC), obtained from industrial bleached Eucalyptus globulus kraft pulp. For that, we exposed co-cultures of human alveolar epithelial A549 cells and THP-1 monocyte-derived macrophages to a concentration range of each CMNM and used the micronucleus (MN) and comet assays. Our results showed that only the lowest concentrations of the CMF sample were able to induce DNA strand breaks (FPG-comet assay). However, none of the three CMNMs produced significant chromosomal alterations (MN assay). These findings, together with results from previous in vitro studies using monocultures of A549 cells, indicate that the tested CNF and CNC are not genotoxic under the conditions tested, while the CMF display a low genotoxic potential.

APA, Harvard, Vancouver, ISO, and other styles

50

Abzianidze, Victoria, Petr Beltyukov, Sofya Zakharenkova, Natalia Moiseeva, Jennifer Mejia, Alvin Holder, Yuri Trishin, Alexander Berestetskiy, and Victor Kuznetsov. "Synthesis and Biological Evaluation of Phaeosphaeride A Derivatives as Antitumor Agents." Molecules 23, no. 11 (November 21, 2018): 3043. http://dx.doi.org/10.3390/molecules23113043.

Full text

Abstract:

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor activity studies were carried out on the HCT-116, PC3, MCF-7, A549, К562, NCI-Н929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All of the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 was potent against six cancer cell lines, HCT-116, PC-3, K562, NCI-H929, Jurkat, and RPMI8226, showing a 47, 13.5, 16, 4, 1.5, and 7-fold increase in anticancer activity comparative to those of etoposide, respectively. Compound 1 possessed selectivity toward the NCI-H929 cell line (IC50 = 1.35 ± 0.69 μM), while product 7 was selective against three cancer cell lines, HCT-116, MCF-7, and NCI-H929, each having IC50 values of 1.65 μM, 1.80 μM and 2.00 μM, respectively.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'A549-Thp-1'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles