POTENTIATION OF FAS- AND TRAIL-MEDIATED APOPTOSIS BY IFN-γ IN A549 LUNG EPITHELIAL CELLS: ENHANCEMENT OF CASPASE-8 EXPRESSION THROUGH IFN-RESPONSE ELEMENT

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

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Galectin-3 is essential for IgE-dependent activation of human basophils by A549 lung epithelial cells

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2019.03.001 ◽

2019 ◽

Vol 144 (1) ◽

pp. 312-315.e1 ◽

Cited By ~ 6

Author(s):

John T. Schroeder ◽

Abiodun A. Adeosun ◽

Danh Do ◽

Anja P. Bieneman

Keyword(s):

Epithelial Cells ◽

Lung Epithelial Cells ◽

Lung Epithelial ◽

Galectin 3 ◽

Human Basophils ◽

A549 Lung

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Cytotoxic Effects of Air Freshener Biocides in Lung Epithelial Cells

Natural Product Communications ◽

10.1177/1934578x1300800929 ◽

2013 ◽

Vol 8 (9) ◽

pp. 1934578X1300800

Author(s):

Jung-Taek Kwon ◽

Mimi Lee ◽

Gun-Baek Seo ◽

Hyun-Mi Kim ◽

Ilseob Shim ◽

...

Keyword(s):

Dna Damage ◽

Epithelial Cells ◽

Cell Viability ◽

Lung Epithelial Cells ◽

Ros Generation ◽

Dependent Manner ◽

Cytotoxic Effects ◽

Lung Epithelial ◽

Dose Dependent ◽

A549 Lung

This study evaluated the cytotoxicity of mixtures of citral (CTR) and either benzisothiazolinone (BIT, Mix-CTR-BIT) or triclosan (TCS, Mix-CTR-TCS) in human A549 lung epithelial cells. We investigated the effects of various mix ratios of these common air freshener ingredients on cell viability, cell proliferation, reactive oxygen species (ROS) generation, and DNA damage. Mix-CTR-BIT and Mix-CTR-TCS significantly decreased the viability of lung epithelial cells and inhibited cell growth in a dose-dependent manner. In addition, both mixtures increased ROS generation, compared to that observed in control cells. In particular, cell viability, growth, and morphology were affected upon increase in the proportion of BIT or TCS in the mixture. However, comet analysis showed that treatment of cells with Mix-CTR-BIT or Mix-CTR-TCS did not increase DNA damage. Taken together, these data suggested that increasing the content of biocides in air fresheners might induce cytotoxicity, and that screening these compounds using lung epithelial cells may contribute to hazard assessment.

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Annexin-A1 promotes RIG-I-dependent signaling and apoptosis via regulation of the IRF3–IFNAR–STAT1–IFIT1 pathway in A549 lung epithelial cells

Cell Death and Disease ◽

10.1038/s41419-020-2625-7 ◽

2020 ◽

Vol 11 (6) ◽

Cited By ~ 3

Author(s):

Gracemary L. R. Yap ◽

Karishma Sachaphibulkij ◽

Sok Lin Foo ◽

Jianzhou Cui ◽

Anna-Marie Fairhurst ◽

...

Keyword(s):

Epithelial Cells ◽

Lung Epithelial Cells ◽

Annexin A1 ◽

Lung Epithelial ◽

A549 Lung

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Opposing Effect by Cytokines on Fas-Mediated Apoptosis in A549 Lung Epithelial Cells

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/ajrcmb.26.1.4285 ◽

2002 ◽

Vol 26 (1) ◽

pp. 58-66 ◽

Cited By ~ 34

Author(s):

Kristin R. Coulter ◽

Andrea Doseff ◽

Patricia Sweeney ◽

Yijie Wang ◽

Clay B. Marsh ◽

...

Keyword(s):

Epithelial Cells ◽

Lung Epithelial Cells ◽

Lung Epithelial ◽

Opposing Effect ◽

A549 Lung

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Evaluation of the Biocompatibility of Ceramic Nanoparticles with A549 Lung Epithelial Cells

Nanoscience and Nanotechnology Letters ◽

10.1166/nnl.2016.2132 ◽

2016 ◽

Vol 8 (4) ◽

pp. 310-315 ◽

Cited By ~ 1

Author(s):

Nozomu Kiyama ◽

Shigeaki Abe ◽

Shuichi Yamagata ◽

Yasuhiro Yoshida ◽

Junichiro Iida

Keyword(s):

Epithelial Cells ◽

Lung Epithelial Cells ◽

Ceramic Nanoparticles ◽

Lung Epithelial ◽

A549 Lung

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Inhibition of acute lethal pulmonary inflammation by the IDO–AhR pathway

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1615280114 ◽

2017 ◽

Vol 114 (29) ◽

pp. E5881-E5890 ◽

Cited By ~ 16

Author(s):

Soung-Min Lee ◽

Ha Young Park ◽

Young-Sill Suh ◽

Eun Hye Yoon ◽

Juyang Kim ◽

...

Keyword(s):

T Cells ◽

Epithelial Cells ◽

Pulmonary Inflammation ◽

Lung Parenchyma ◽

Lung Epithelial Cells ◽

Dependent Manner ◽

Independent Manner ◽

Hematopoietic Stem ◽

Lung Epithelial ◽

Ifn Γ

The lung is a prototypic organ that was evolved to reduce immunopathology during the immune response to potentially hazardous endogenous and exogenous antigens. In this study, we show that donor CD4+ T cells transiently induced expression of indoleamine 2,3-dioxygenase (IDO) in lung parenchyma in an IFN-γ–dependent manner early after allogeneic hematopoietic stem cell transplantation (HSCT). Abrogation of host IDO expression by deletion of the IDO gene or the IFN-γ gene in donor T cells or by FK506 treatment resulted in acute lethal pulmonary inflammation known as idiopathic pneumonia syndrome (IPS). Interestingly, IL-6 strongly induced IDO expression in an IFN-γ–independent manner when deacetylation of STAT3 was inhibited. Accordingly, a histone deacetylase inhibitor (HDACi) could reduce IPS in the state where IFN-γ expression was suppressed by FK506. Finally, l-kynurenine produced by lung epithelial cells and alveolar macrophages during IPS progression suppresses the inflammatory activities of lung epithelial cells and CD4+ T cells through the aryl hydrocarbon receptor pathway. Taken together, our results reveal that IDO is a critical regulator of acute pulmonary inflammation and that regulation of IDO expression by HDACi may be a therapeutic approach for IPS after HSCT.

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