scholarly journals β2-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence

2017 ◽  
Vol 312 (5) ◽  
pp. L669-L677 ◽  
Author(s):  
Na Gao ◽  
Ying Wang ◽  
Chun-Ming Zheng ◽  
Yan-Li Gao ◽  
Hui Li ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
A549 Cells ◽  
Cell Senescence ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cell ◽  
Class I Mhc ◽  
Mhc I ◽  
Lung Emphysema ◽  
Lung Epithelial

β2-Microglobulin (β2M), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of β2M in the development of lung emphysema. Here, we found that concentrations of β2M in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 vs. 1.42 ± 0.06 mg/l, P < 0.01). Moreover, the expression of β2M was significantly higher in lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%, P < 0.01). Immunofluorescence showed that β2M was mainly expressed in prosurfactant protein C-positive (pro-SPC+) alveolar epithelial cells and CD14+ macrophages. Exposure to recombinant human β2M and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-β2M antibody. However, anti-β2M antibody did not attenuate the elevated production of IL-1β, IL-6, and TNF-α in A549 cells that were exposed to CSE. Immunofluorescence showed that colocalization of β2M, and the hemochromatosis gene (HFE) protein was observed on A549 cells. These data suggest β2M might participate in the development of lung emphysema through induction of lung epithelial cell senescence and inhibition.

scholarly journals Cell culture model system utilizing engineered A549 cells to express high levels of ACE2 and TMPRSS2 for investigating SARS-CoV-2 infection and antivirals

2022 ◽  
Author(s):  
Ching-Wen Chang ◽  
Krishna Mohan Parsi ◽  
Mohan Somasundaran ◽  
Emma Vanderleeden ◽  
John Cruz ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Virus Infection ◽  
Viral Entry ◽  
Human Lung ◽  
A549 Cells ◽  
Model System ◽  
Lung Epithelial Cell ◽  
Clinical Feature ◽  
Lung Epithelial

Novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an imminent global threat since its initial outbreak in December 2019. A simple in vitro model system using cell lines highly susceptible to SARS-CoV-2 infection are critical to facilitate the study of the virus cycle and to discover effective antivirals against the virus. Human lung alveolar A549 cells are regarded as a useful and valuable model for respiratory virus infection. However, SARS-CoV-2 uses the ACE2 as receptor for viral entry and the TMPRSS2 to prime the Spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a robust human lung epithelial cell-based model by transducing ACE2 and TMPRSS2 into A549 cells and show that the ACE2 enriched A549ACE2/TMPRSS2 cells (ACE2plus) and its single-cell-derived subclone (ACE2plusC3) are highly susceptible to SARS-CoV-2 infection. These engineered ACE2plus showed higher ACE2 and TMPRSS2 mRNA expression levels than currently used Calu3 and commercial A549ACE2/TMPRSS2 cells. ACE2 and TMPRSS2 proteins were also highly and ubiquitously expressed in ACE2plusC3 cells. Additionally, antiviral drugs like Camostat mesylate, EIDD-1931, and Remdesivir strongly inhibited SARS-CoV-2 replication. Notably, multinucleated syncytia, a clinical feature commonly observed in severe COVID-19 patients was induced in ACE2plusC3 cells either by virus infection or by overexpressing the Spike proteins of different variants of SARS-CoV-2. Syncytial process was effectively blocked by the furin protease inhibitor, Decanoyl-RVKR-CMK. Taken together, we have developed a robust human A549 lung epithelial cell-based model that can be applied to probe SARS-CoV-2 replication and to facilitate the discovery of SARS-CoV-2 inhibitors.

Effect of curcumin on lung epithelial injury and ferroptosis induced by cigarette smoke

2021 ◽  
pp. 096032712110594
Author(s):  
Xin Tang ◽  
Zhenyu Li ◽  
Zhi Yu ◽  
Jinna Li ◽  
Jinbang Zhang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cigarette Smoke ◽  
Cell Injury ◽  
Lavage Fluid ◽  
Lung Epithelial Cell ◽  
Control Group ◽  
Epithelial Injury ◽  
Lung Epithelial

Cigarette smoke (CS)-caused ferroptosis was involved in the pathogenesis of COPD, but the role of ferroptosis in lung epithelial injury and inflammation is not clear. Rats were treated with CS or CUR and BEAS-2B cells were exposed to CS extract (CSE), ferrostatin-1 (Fer-1), deferoxamine (DFO), or CUR to detect reactive oxygen species (ROS) accumulation, lipid peroxidation, iron overload, and ferroptosis-related protein, which were the characteristic changes of ferroptosis. Compared with the control group, CSE-treated BEAS-2B cells had more cell death, higher cytotoxicity, and lower cell viability. The infiltration of inflammatory cell around the bronchi in the CS group of rats was more than that in the normal group. Meanwhile, CSE/CS elevated the levels of interleukin-6 and tumor necrosis factor-α in BEAS-2B cells and bronchoalveolar lavage fluid of rats. Besides, accumulative ROS and depleted glutathione was observed in vitro. In BEAS-2B cells and lung tissues of rats, CSE/CS increased malondialdehyde and iron; down-regulated solute carrier family 7, glutathione peroxidase 4, and ferritin heavy chain levels; and up-regulated transferrin receptor level. These changes were rescued by pretreatment of Fer-1 or DFO in vitro, and mitigated by CUR in vitro and in vivo. Collectively, this study reveals that ferroptosis was involved in lung epithelial cell injury and inflammation induced by CS, and CUR may alleviate CS-induced injury, inflammation, and ferroptosis of lung epithelial cell.

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