Grape Seed Proanthocyanidin Inhibits Mucin Synthesis and Viral Replication by Suppression of AP-1 and NF-κB via p38 MAPKs/JNK Signaling Pathways in Respiratory Syncytial Virus-Infected A549 Cells

2017 ◽  
Vol 65 (22) ◽  
pp. 4472-4483 ◽  
Author(s):  
Jin-Woo Lee ◽  
Young Il Kim ◽  
Chang-Nim Im ◽  
Sung Wan Kim ◽  
Su Jin Kim ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Replication ◽  
Signaling Pathways ◽  
A549 Cells ◽  
Grape Seed ◽  
Jnk Signaling ◽  
Mucin Synthesis ◽  
Grape Seed Proanthocyanidin ◽  
Syncytial Virus ◽  
P38 Mapks

Respiratory syncytial virus increases IL-8 gene expression and protein release in A549 cells

1995 ◽  
Vol 269 (6) ◽  
pp. L865-L872 ◽  
Author(s):  
M. A. Fiedler ◽  
K. Wernke-Dollries ◽  
J. M. Stark
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Viral Replication ◽  
Mrna Expression ◽  
A549 Cells ◽  
Protein Release ◽  
Tnf Alpha ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Syncytial Virus

The mechanism of respiratory syncytial virus (RSV)-induced inflammation in the airways of infants and children is not fully understood. We hypothesized that RSV directly induces interleukin (IL)-8 gene expression in airway epithelial cells, independent of IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) production. Exposure of A549 cells (an airway epithelial cell line) to RSV resulted in increased IL-8 mRNA expression and IL-8 protein release from the cells as early as 2 h after treatment. Neither IL-1 beta nor TNF-alpha (mRNA or protein) were detected. Viral replication was not necessary for the effects of RSV on IL-8 mRNA expression and protein release early in the infectious process. However, sustained levels of increased IL-8 production required RSV replication. A dose-response relationship was observed between the multiplicity of infection and IL-8 production with both active and nonreplicative RSV at the 2-h time point. Both active RSV and nonreplicative RSV increased the transcriptional activity of the 1.6-kb 5' flanking region of the IL-8 gene. Neither active RSV nor nonreplicative RSV increased the stability of the IL-8 mRNA in A549 cells. We conclude that RSV increases IL-8 gene expression in A549 cells in a biphasic pattern independent of viral replication early (2 h) but dependent on viral replication late (24 h).

scholarly journals Respiratory Syncytial Virus-Inducible BCL-3 Expression Antagonizes the STAT/IRF and NF-κB Signaling Pathways by Inducing Histone Deacetylase 1 Recruitment to the Interleukin-8 Promoter

2005 ◽  
Vol 79 (24) ◽  
pp. 15302-15313 ◽  
Author(s):  
Mohammad Jamaluddin ◽  
Sanjeev Choudhary ◽  
Shaofei Wang ◽  
Antonella Casola ◽  
Ruksana Huda ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Signaling Pathways ◽  
Histone Deacetylase ◽  
Trichostatin A ◽  
A549 Cells ◽  
B Cell Lymphoma ◽  
Interleukin 8 ◽  
Nuclear Targeting ◽  
Histone Deacetylase 1 ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a paramyxovirus that produces airway inflammation, in part by inducing interleukin-8 (IL-8) expression, a CXC-type chemokine, via the NF-κB/RelA and STAT/IRF signaling pathways. In RSV-infected A549 cells, IL-8 transcription attenuates after 24 h in spite of ongoing viral replication and persistence of nuclear RelA, suggesting a mechanism for transcriptional attenuation. RSV infection induces B-cell lymphoma protein -3 (Bcl-3) expression 6 to 12 h after viral infection, at times when IL-8 transcription is inhibited. By contrast, 293 cells, deficient in inducible Bcl-3 expression, show no attenuation of IL-8 transcription. We therefore examined Bcl-3's role in terminating virus-inducible IL-8 transcription. Transient expression of Bcl-3 potently inhibited virus-inducible IL-8 transcription by disrupting both the NF-κB and STAT/IRF pathways. Although previously Bcl-3 was thought to capture 50-kDa NF-κB1 isoforms in the cytoplasm, immunoprecipitation (IP) and electrophoretic mobility shift assays indicate that nuclear Bcl-3 associates with NF-κB1 without affecting DNA binding. Additionally, Bcl-3 potently inhibited the STAT/IRF pathway. Nondenaturing co-IP assays indicate that nuclear Bcl-3 associates with STAT-1 and histone deacetylase 1 (HDAC-1), increasing HDAC-1 recruitment to the IL-8 promoter. Treatment with the HDAC inhibitor trichostatin A blocks attenuation of IL-8 transcription. A nuclear targeting-deficient Bcl-3 is unable to enhance HDAC-1-mediated chemokine repression. Finally, small inhibitory RNA-mediated Bcl-3 “knockdown” resulted in enhanced RSV-induced chemokine expression in A549 cells. These data indicate that Bcl-3 is a virus-inducible inhibitor of chemokine transcription by interfering with the NF-κB and STAT/IRF signaling pathways by complexing with them and recruiting HDAC-1 to attenuate target promoter activity.

scholarly journals Differential Role for TLR3 in Respiratory Syncytial Virus-Induced Chemokine Expression

2005 ◽  
Vol 79 (6) ◽  
pp. 3350-3357 ◽  
Author(s):  
Brian D. Rudd ◽  
Ezra Burstein ◽  
Colin S. Duckett ◽  
Xiaoxia Li ◽  
Nicholas W. Lukacs
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Viral Replication ◽  
Signaling Pathways ◽  
Rna Virus ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Chemokine Production ◽  
Young Infants ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young infants worldwide. Previous studies have reported that the induction of interleukin-8/CXCL8 and RANTES/CCL5 correlates with disease severity in humans. The production of these chemokines is elicited by viral replication and is NF-κB dependent. RSV, a negative-sense single-stranded RNA virus, requires full-length positive-sense RNA for synthesis of new viral RNA. The aim of our studies was to investigate whether active viral replication by RSV could evoke chemokine production through TLR3-mediated signaling pathways. In TLR3-transfected HEK 293 cells, live RSV preferentially activated chemokines in both a time- and dose-dependent manner compared to vector controls. RSV was also shown to upregulate TLR3 in human lung fibroblasts and epithelial cells (MRC-5 and A549). Targeting the expression of TLR3 with small interfering RNA decreased synthesis of IP-10/CXCL10 and CCL5 but did not significantly reduce levels of CXCL8. Blocking the expression of the adapter protein MyD88 established a role for MyD88 in CXCL8 production, whereas CCL5 synthesis was found to be MyD88 independent. Production of CCL5 by RSV was induced directly through TLR3 signaling pathways and did not require interferon (IFN) signaling through the IFN-α/β receptor. TLR3 did not affect viral replication, since equivalent viral loads were recovered from RSV-infected cells despite altered TLR3 expression. Taken together, our studies indicate that TLR3 mediates inflammatory cytokine and chemokine production in RSV-infected epithelial cells.

Mechanism of RSV-induced IL-8 gene expression in A549 cells before viral replication

1996 ◽  
Vol 271 (6) ◽  
pp. L963-L971 ◽  
Author(s):  
M. A. Fiedler ◽  
K. Wernke-Dollries ◽  
J. M. Stark
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Viral Replication ◽  
Transcriptional Activation ◽  
Mutational Analysis ◽  
A549 Cells ◽  
Nf Kappa B ◽  
Mobility Shift ◽  
Syncytial Virus ◽  
Time Point

Previous studies demonstrated that respiratory syncytial virus (RSV) infection of A549 cells induced interleukin (IL)-8 gene expression and protein release from the cells as early as 2 h after treatment [M. A. Fiedler, K. Wernke-Dollries, and J. M. Stark. Am. J. Physiol. 269 (Lung Cell. Mol. Physiol. 13): L865-L872, 1995; J. G. Mastronarde, M. M. Monick, and G. W. Hunninghake. Am. J. Respir. Cell Mol. Biol. 13: 237-244, 1995]. Furthermore, the effects of RSV at the 2-h time point were not dependent on viral replication. The studies reported here were designed to test the hypothesis that active and inactive RSV induce IL-8 gene expression in A549 cells at the 2-h time point by a mechanism dependent on the activation of the nuclear transcription factor NF-kappa B Northern blot analysis indicated that IL-8 gene expression occurred independent of protein synthesis 2 h after A549 cells were treated with RSV. Analysis of nuclear extracts from RSV-treated A549 cells by electrophoretic mobility shift assays demonstrated that NF-kappa B was activated as early as 15 min after RSV was added to the cells and remained activated for at least 90 min. In contrast, baseline levels of NF-IL-6 and activator protein-1 (AP-1) did not change over this period of time. Deoxyribonuclease footprint analysis of a portion of the 5'-flanking region of the IL-8 gene demonstrated two potential regions for transcription factor binding, which corresponded to the potential AP-1 binding site, and potential NF-IL-6 and NF-kappa B binding sites. Mutational analysis of the 200-bp 5'-untranslated region of the IL-8 gene demonstrated that activation of NF-kappa B and NF-IL-6 were required for RSV-induced transcriptional activation of the IL-8 gene.

scholarly journals Induction of IL-6 and CCL5 (RANTES) in human respiratory epithelial (A549) cells by clinical isolates of respiratory syncytial virus is strain specific

2012 ◽  
Vol 9 (1) ◽  
pp. 190 ◽  
Author(s):  
Ruth Levitz ◽  
Rachel Wattier ◽  
Pamela Phillips ◽  
Alexandra Solomon ◽  
Jessica Lawler ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
A549 Cells ◽  
Clinical Isolates ◽  
Syncytial Virus ◽  
Respiratory Epithelial ◽  
Is Strain

scholarly journals Respiratory syncytial virus-A dynamics and the effects of lumicitabine, a nucleoside viral replication inhibitor, in experimentally infected humans

2018 ◽  
Vol 74 (2) ◽  
pp. 442-452 ◽  
Author(s):  
Kashyap Patel ◽  
Carl M Kirkpatrick ◽  
Keith A Nieforth ◽  
Sushmita Chanda ◽  
Qingling Zhang ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Replication ◽  
Replication Inhibitor ◽  
Syncytial Virus
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