Cell line A549 as a model of the type II pneumocyte

Nardone, Linda L.; Andrews, S. Brian

doi:10.1016/0005-2760(79)90061-4

Cited by 69 publications

(23 citation statements)

References 35 publications

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“…To further investigate whether similar mechanisms are involved in radiation-induced EMT in AE2, we examined the effects of radiation using A549 cells, a human lung cancer cell line with characteristics of AE2 cells [28, 29]. Irradiating A549 cells resulted in a time-dependent increase in the protein levels of α-SMA at both 24 and 48 h postirradiation; E-cadherin levels were reduced 48 hours after radiation (Fig.…”

Section: Resultsmentioning

confidence: 99%

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ERK/GSK3β/Snail signaling mediates radiation-induced alveolar epithelial-to-mesenchymal transition

Nagarajan

Melo

Deng

et al. 2012

Free Radical Biology and Medicine

113

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Radiotherapy is one of the major treatment regimes for thoracic malignancies, but can lead to severe lung complications including pneumonitis and fibrosis. Recent studies suggest that epithelial to mesenchymal transition (EMT) plays an important role in tissue injury leading to organ fibrosis. To investigate whether radiation can induce EMT in lung epithelial cells and also understand the potential mechanism(s) associated with this change, rat alveolar type II lung epithelial RLE-6TN cells were irradiated with 8 Gy of 137Cs γ-rays. Western blot and immunofluorescence analyses revealed a time-dependent decrease in E-cadherin with a concomitant increase in α-SMA and vimentin after radiation, suggesting that the epithelial cells acquired mesenchymal-like morphology. Protein levels and nuclear translocation of Snail, the key inducer of EMT, were significantly elevated in the irradiated cells. Radiation also induced a time-dependent inactivation of glycogen synthase kinase-3β (GSK3ß), an endogenous inhibitor of Snail. A marked increase in phosphorylation of ERK1/2, but not JNKs or p38, was observed in irradiated RLE-6TN cells. Silencing ERK1/2 using siRNAs and the MEK/ERK inhibitor U0126 attenuated the radiation-induced phosphorylation of GSK3ß and altered the protein levels of Snail, α-SMA and E-cadherin in RLE-6TN cells. Pre-incubating RLE-6TN cells with N-acetyl cysteine, an antioxidant, abolished the radiation-induced phosphorylation of ERK and altered protein levels of Snail, E-cadherin and α-SMA. These findings reveal, for the first time, that radiation-induced EMT in alveolar type II epithelial cells is mediated by the ERK/GSK3ß/Snail pathway.

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Section: Resultsmentioning

confidence: 99%

“…A549 cells have been used as a model of AE2 cells to study drug metabolism [28, 29] and other biological events, i.e. EMT [52].…”

Section: Discussionmentioning

confidence: 99%

ERK/GSK3β/Snail signaling mediates radiation-induced alveolar epithelial-to-mesenchymal transition

Nagarajan

Melo

Deng

et al. 2012

Free Radical Biology and Medicine

113

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“…However, conflicting results about its suitability as ATII cell model have been reported [24,25]. It has been shown that extended cultivation of A549 cells leads to reduced proliferation and promotion of the ATII cell phenotype, as evidenced by high numbers of multilamellar bodies (a typical sign of ATII cells) with similar contents of phospholipids than those found in primary lung tissue [22,74]. Moreover, mRNA gene expression profiling and its comparison with primary cultures of ATII cells suggests a more ATII-like phenotype of A549 cells after long-term cultivation [22].…”

Section: Discussionmentioning

confidence: 99%

Short-Term versus Long-Term Culture of A549 Cells for Evaluating the Effects of Lipopolysaccharide on Oxidative Stress, Surfactant Proteins and Cathelicidin LL-37

Nová

Škovierová

Strnádel

et al. 2020

IJMS

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Alveolar epithelial type II (ATII) cells and their proper function are essential for maintaining lung integrity and homeostasis. However, they can be damaged by lipopolysaccharide (LPS) during Gram-negative bacterial infection. Thus, this study evaluated and compared the effects of LPS on short and long-term cultures of A549 cells by determining the cell viability, levels of oxidative stress and antimicrobial peptide cathelicidin LL-37 and changes in the expression of surfactant proteins (SPs). Moreover, we compared A549 cell response to LPS in the presence of different serum concentrations. Additionally, the effect of N-acetylcysteine (NAC) on LPS-induced oxidative stress as a possible treatment was determined. Our results indicate that A549 cells are relatively resistant to LPS and able to maintain integrity even at high LPS concentrations. Their response to endotoxin is partially dependent on serum concentration. NAC failed to lower LPS-induced oxidative stress in A549 cells. Finally, LPS modulates SP gene expression in A549 cells in a time dependent manner and differences between short and long-term cultures were present. Our results support the idea that long-term cultivation of A549 cells could promote a more ATII-like phenotype and thus could be a more suitable model for ATII cells, especially for in vitro studies dealing with surfactant production.

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“…We measure both ROS production in the cells and the cell viability using two separate assays. We utilize the A549 epithelial cell line, which is frequently used in toxicity studies [50-52]. It was first cultured in 1972 from the cancerous lung tissue of a 58 year old man.…”

Section: Introductionmentioning

confidence: 99%

Quantification of particle-induced inflammatory stress response: a novel approach for toxicity testing of earth materials

2012

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BackgroundReactive oxygen species (ROS) are vital regulators of many cellular functions in the body. The intracellular ROS concentration is highly regulated by a balance between pro-oxidants and anti-oxidants. A chronic excess of pro-oxidants leads to elevated ROS concentrations and inflammation, possibly initiating or enhancing disease onset. Mineral-induced generation of ROS, the role of minerals in upregulating cellular ROS, and their role in the development of several occupational diseases are now widely recognized. However, there is no standard protocol to determine changes in ROS production in cells after exposure to mineral dust or earth materials in general. In this study, a new method for determining the degree of cellular toxicity (i.e., cytotoxicity) of particles is described that will help bridge the gap in knowledge.ResultsBy measuring the production of ROS and the viability of cells, an inflammatory stress response (ISR) indicator is defined. This approach normalizes the ROS upregulation with respect to the number of viable cells at the time of measurement. We conducted experiments on a series of minerals and soils that represent materials that are inert (i.e., glass beads, anatase, and a soil with low trace element content), moderately reactive (i.e., soil with high trace element content), and highly reactive (i.e., pyrite). Inert materials generated the lowest ISR, averaging 350% compared to the control. Acid washed pyrite produced the highest ISR (1,100 fold higher than the control). The measurements conducted as a function of time showed a complex response. Most materials showed an increase in ISR with particle loading.ConclusionsThe amount of cellularly generated ROS and cell viability combined provide a better understanding of particle-induced oxidative stress. The results indicate that some earth materials may solicit an initial burst of ROS, followed by a second phase in which cell viability decreases and ROS production increases, leading to a high ISR value. Hence, measurements conducted over a range of particle loading combined with multiple data measurements up to 24 hours can provide new insights in the possible effect of exposure to earth materials on human health.

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Cell line A549 as a model of the type II pneumocyte

Cited by 69 publications

References 35 publications

ERK/GSK3β/Snail signaling mediates radiation-induced alveolar epithelial-to-mesenchymal transition

ERK/GSK3β/Snail signaling mediates radiation-induced alveolar epithelial-to-mesenchymal transition

Short-Term versus Long-Term Culture of A549 Cells for Evaluating the Effects of Lipopolysaccharide on Oxidative Stress, Surfactant Proteins and Cathelicidin LL-37

Quantification of particle-induced inflammatory stress response: a novel approach for toxicity testing of earth materials

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