scholarly journals IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 548 ◽  
Author(s):  
Susann Kummer ◽  
Ori Avinoam ◽  
Hans-Georg Kräusslich
Keyword(s):  
Epithelial Cells ◽  
Influenza A ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Human Lung Epithelial Cell ◽  
Human Airway ◽  
Lung Epithelial ◽  
Endosomal Vesicles ◽  
Human Airway Epithelial Cells

Interferon-induced transmembrane proteins (IFITMs) have been shown to strongly affect influenza A virus (IAV) infectivity in tissue culture. Moreover, polymorphisms in IFITM3 have been associated with the severity of the disease in humans. IFITM3 appears to act early in the infection, but its mechanism of action and potential interactions with incoming IAV structures are not yet defined. Here, we visualized endogenous IFITM3 interactions with IAV in the human lung epithelial cell line A549 and in primary human airway epithelial cells employing stimulated emission depletion super-resolution microscopy. By applying an iterative approach for the cluster definition and computational cluster analysis, we found that IFITM3 reorganizes into clusters as IAV infection progresses. IFITM3 cluster formation started at 2-3 h post infection and increased over time to finally coat IAV-containing endosomal vesicles. This IAV-induced phenotype was due to the endosomal recruitment of IFITM3 rather than to an overall increase in the IFITM3 abundance. While the IAV-induced IFITM3 clustering and localization to endosomal vesicles was comparable in primary human airway epithelial cells and the human lung epithelial cell line A549, the endogenous IFITM3 signal was higher in primary cells. Moreover, we observed IFITM3 signals adjacent to IAV-containing recycling endosomes.

Infection of cultured human airway epithelial cells by influenza a virus

Life Sciences ◽  
1991 ◽  
Vol 49 (16) ◽  
pp. 1173-1181 ◽  
Author(s):  
Theodore F. Reiss ◽  
Dieter C. Gruenert ◽  
Jay A. Nadel ◽  
David B. Jacoby
Keyword(s):  
Epithelial Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

scholarly journals Adaptation of influenza A (H7N9) virus in primary human airway epithelial cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Daniel Tsung-Ning Huang ◽  
Chun-Yi Lu ◽  
Ya-Hui Chi ◽  
Wan-Ling Li ◽  
Luan-Yin Chang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Influenza A ◽  
Airway Epithelial Cells ◽  
H7n9 Virus ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Zn2+-induced IL-8 expression involves AP-1, JNK, and ERK activities in human airway epithelial cells

2006 ◽  
Vol 290 (5) ◽  
pp. L1028-L1035 ◽  
Author(s):  
Yu-Mee Kim ◽  
William Reed ◽  
Weidong Wu ◽  
Philip A. Bromberg ◽  
Lee M. Graves ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Promoter Activity ◽  
Fluorescent Protein ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Human Airway ◽  
Mrna And Protein Expression ◽  
Human Airway Epithelial Cells

Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. IL-8 is an important proinflammatory cytokine in the human lung and is induced in human airway epithelial cells exposed to zinc. In this study, we examined the cellular mechanisms responsible for Zn2+-induced IL-8 expression. Zn2+ stimulation resulted in pronounced increases in both IL-8 mRNA and protein expression in the human airway epithelial cell line (BEAS-2B). IL-8 promoter activity was significantly increased by Zn2+ exposure in BEAS-2B cells, indicating that Zn2+-induced IL-8 expression is transcriptionally mediated. Mutation of the activating protein (AP)-1 response element in an IL-8 promoter-enhanced green fluorescent protein construct reduced Zn2+-induced IL-8 promoter activity. Moreover, Zn2+ exposure of BEAS-2B cells induced the phosphorylation of the AP-1 proteins c-Fos and c-Jun. We observed that Zn2+ exposure induced the phosphorylation of ERK, JNK, and p38 MAPKs, whereas inhibition of ERK or JNK activity blocked IL-8 mRNA and protein expression in BEAS-2B cells treated with Zn2+. In addition, we investigated the role of protein tyrosine phosphatases in the activation of signaling by Zn2+. Zn2+ treatment inhibited ERK- and JNK-directed phosphatase activities in BEAS-2B cells. These results suggested that Zn2+-induced inhibition of phosphatase activity is an initiating event in MAPK and AP-1 activation that leads to enhanced IL-8 expression by human airway epithelial cells.

Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection

2005 ◽  
Vol 289 (1) ◽  
pp. L85-L95 ◽  
Author(s):  
Jason C. L. Spurrell ◽  
Shahina Wiehler ◽  
Raza S. Zaheer ◽  
Scherer P. Sanders ◽  
David Proud
Keyword(s):  
Epithelial Cells ◽  
Primary Cultures ◽  
Airway Epithelial Cells ◽  
Human Rhinovirus ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Human rhinovirus (HRV) infections trigger exacerbations of asthma and chronic obstructive pulmonary disease (COPD) and are associated with lymphocytic infiltration of the airways. We demonstrate that infection of primary cultures of human airway epithelial cells, or of the BEAS-2B human bronchial epithelial cell line, with human rhinovirus type 16 (HRV-16) induces expression of CXCL10 [IFN-γ-inducible protein 10 (IP-10)], a ligand for the CXCR3 receptor found on activated type 1 T lymphocytes and natural killer cells. IP-10 mRNA reached maximal levels 24 h after HRV-16 infection then declined, whereas protein levels peaked 48 h after infection with no subsequent new synthesis. Cytosolic levels of AU-rich factor 1, a protein associated with mRNA destabilization, increased beginning 24 h after HRV-16 infection. Generation of IP-10 required virus capable of replication but was not dependent on prior induction of type 1 interferons. Transfection of synthetic double-stranded RNA into epithelial cells induced robust production of IP-10, whereas transfection of single-stranded RNA had no effect. Induction of IP-10 gene expression by HRV-16 depended upon activation of NF-κB, as well as other transcription factor recognition sequences further upstream in the IP-10 promoter. In vivo infection of human volunteers with HRV-16 strikingly increased IP-10 protein in nasal lavages during symptomatic colds. Levels of IP-10 correlated with symptom severity, viral titer, and numbers of lymphocytes in airway secretions. Thus IP-10 may play a role in the pathogenesis of HRV-induced colds and in HRV-induced exacerbations of COPD and asthma.

Proteasome inhibition induces TNFR1 shedding from human airway epithelial (NCI-H292) cells

2005 ◽  
Vol 289 (2) ◽  
pp. L233-L243 ◽  
Author(s):  
Stewart J. Levine ◽  
Barbara Adamik ◽  
Feras I. Hawari ◽  
Aminul Islam ◽  
Zu-Xi Yu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Umbilical Vein ◽  
Primary Cultures ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Human Airway ◽  
Zinc Metalloprotease ◽  
Human Airway Epithelial Cells

The type 1 55-kDa TNF receptor (TNFR1) is an important modulator of lung inflammation. Here, we hypothesized that the proteasome might regulate TNFR1 shedding from human airway epithelial cells. Treatment of NCI-H292 human airway epithelial cells for 2 h with the specific proteasome inhibitor clasto-lactacystin β-lactone induced the shedding of proteolytically cleaved TNFR1 ectodomains. Clasto-lactacystin β-lactone also induced soluble TNFR1 (sTNFR1) release from the A549 pulmonary epithelial cell line, as well as from primary cultures of human small airway epithelial cells and human umbilical vein endothelial cells. Furthermore, sTNFR1 release induced by clasto-lactacystin β-lactone was not a consequence of apoptosis or the extracellular release of TNFR1 exosome-like vesicles. The clasto-lactacystin β-lactone-induced increase in TNFR1 shedding was associated with reductions in cell surface receptors and intracytoplasmic TNFR1 stores that were primarily localized to vesicular structures. As expected, the broad-spectrum zinc metalloprotease inhibitor TNF-α protease inhibitor 2 (TAPI-2) attenuated clasto-lactacystin β-lactone-mediated TNFR1 shedding, which is consistent with its ability to inhibit the zinc metalloprotease-catalyzed cleavage of TNFR1 ectodomains. TAPI-2 also reduced TNFR1 on the cell surface and attenuated the clasto-lactacystin β-lactone-induced reduction of intracytoplasmic TNFR1 vesicles. This suggests that TNFR1 shedding induced by clasto-lactacystin β-lactone involves the zinc metalloprotease-dependent trafficking of intracytoplasmic TNFR1 vesicles to the cell surface. Together, these data are consistent with the conclusion that proteasomal activity negatively regulates TNFR1 shedding from human airway epithelial cells, thus identifying previously unrecognized roles for the proteasome and zinc metalloproteases in modulating the generation of sTNFRs.

scholarly journals Cation currents in human airway epithelial cells induced by infection with influenza A virus

2009 ◽  
Vol 587 (13) ◽  
pp. 3159-3173 ◽  
Author(s):  
M. Gallacher ◽  
S. G. Brown ◽  
B. G. Hale ◽  
R. Fearns ◽  
R. E. Olver ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Leptin enhances ICAM-1 expression, induces migration and cytokine synthesis, and prolongs survival of human airway epithelial cells

2015 ◽  
Vol 309 (8) ◽  
pp. L801-L811 ◽  
Author(s):  
Maho Suzukawa ◽  
Rikiya Koketsu ◽  
Shintaro Baba ◽  
Sayaka Igarashi ◽  
Hiroyuki Nagase ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Epithelial Cells ◽  
Quantitative Pcr ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Human Airway ◽  
Enhanced Production ◽  
Cytokine Analysis ◽  
Human Airway Epithelial Cells

There is rising interest in how obesity affects respiratory diseases, since epidemiological findings indicate a strong relationship between the two conditions. Leptin is a potent adipokine produced mainly by adipocytes. It regulates energy storage and expenditure and also induces inflammation. Previous studies have shown that leptin is able to activate inflammatory cells such as lymphocytes and granulocytes, but little is known about its effect on lung structural cells. The present study investigated the effects of leptin on human airway epithelial cells by using human primary airway epithelial cells and a human airway epithelial cell line, BEAS-2B. Flow cytometry showed enhanced ICAM-1 expression by both of those cells in response to leptin, and that effect was abrogated by dexamethasone or NF-κB inhibitor. Flow cytometry and quantitative PCR showed that airway epithelial cells expressed leptin receptor (Ob-R), whose expression level was downregulated by leptin itself. Multiplex cytokine analysis demonstrated enhanced production of CCL11, G-CSF, VEGF, and IL-6 by BEAS-2B cells stimulated with leptin. Furthermore, transfection of Ob-R small interference RNA decreased the effect of leptin on CCL11 production as assessed by quantitative PCR. Finally, leptin induced migration of primary airway epithelial cells toward leptin, suppressed BEAS-2B apoptosis induced with TNF-α and IFN-γ, and enhanced proliferation of primary airway epithelial cells. In summary, leptin was able to directly activate human airway epithelial cells by binding to Ob-R and by NF-κB activation, resulting in upregulation of ICAM-1 expression, induction of CCL11, VEGF, G-CSF, and IL-6 synthesis, induction of migration, inhibition of apoptosis, and enhancement of proliferation.

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