scholarly journals Autocrine Regulation and Experimental Modulation of Interleukin-6 Expression by Human Pulmonary Epithelial Cells Infected with Respiratory Syncytial Virus

1998 ◽  
Vol 72 (3) ◽  
pp. 2496-2499 ◽  
Author(s):  
Zili Jiang ◽  
Masaru Kunimoto ◽  
Janak A. Patel
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Cell Cultures ◽  
Interleukin 6 ◽  
Neutralizing Antibodies ◽  
Antiviral Agent ◽  
Significant Inhibition ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Syncytial Virus

ABSTRACT The mechanisms of regulation of interleukin-6 (IL-6) production in respiratory syncytial virus (RSV)-infected respiratory epithelial cells were evaluated in A549 cell cultures. Incubation with purified RSV resulted in significant production of IL-1α, IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α). Addition of saturating concentrations of neutralizing antibodies against IL-1α, IL-1β, or TNF-α into purified RSV-infected cell cultures resulted in a significant inhibition of IL-6 production, although anti-IL-1α antibody had the most predominant effect (80% inhibition). Anti-IL-1α antibody also almost completely blocked the expression of mRNA for IL-6. Addition of therapeutic concentrations of dexamethasone (1 μM) or ribavirin (90 μg/ml), an antiviral agent, also significantly inhibited the synthesis of IL-6. Hence, in clinical settings, pharmacological agents such as the specific antagonists of IL-6-inducing cytokines, as well as dexamethasone and ribavirin, could be used to modulate IL-6 production.

scholarly journals Incomplete Regulation of NF-κB by IκBα during Respiratory Syncytial Virus Infection in A549 Cells

1999 ◽  
Vol 73 (5) ◽  
pp. 4502-4507 ◽  
Author(s):  
Michael A. Fiedler ◽  
Kara Wernke-Dollries
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Inhibitory Effect ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) infection of airway epithelial cells results in persistent NF-κB activation and NF-κB-mediated interleukin-8 production. Previous studies in airway epithelial cells demonstrated that tumor necrosis factor alpha (TNF-α)-induced NF-κB activation is transient due to regulation by IκBα. However, during RSV infection, IκBα has only a partial inhibitory effect on NF-κB activation. Studies presented here demonstrate that neither increased IκBα production which occurs as a result of RSV-induced NF-κB activation nor inhibition of proteasome-mediated IκBα degradation results in a reversal of RSV-induced NF-κB activation. Thus, while manipulation of IκBα results in reversal of TNF-α-induced NF-κB activation, manipulation of IκBα does not result in a reversal of RSV-induced NF-κB activation.

Dual mechanism forMycobacterium tuberculosiscytotoxicity on lung epithelial cells

2012 ◽  
Vol 58 (7) ◽  
pp. 909-916 ◽  
Author(s):  
Jorge Castro-Garza ◽  
W. Edward Swords ◽  
Russell K. Karls ◽  
Frederick D. Quinn
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Neutralizing Antibodies ◽  
Cytotoxic Effect ◽  
Alveolar Epithelial Cell ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Lung Epithelial

Mycobacterium tuberculosis strains CDC1551 and Erdman were used to assess cytotoxicity in infected A549 human alveolar epithelial cell monolayers. Strain CDC1551 was found to induce qualitatively greater disruption of A549 monolayers than was strain Erdman, although total intracellular and cell-associated bacterial growth rates over the course of the infections were not significantly different. Cell-free culture supernatants from human monocytic cells infected with either of the 2 M. tuberculosis strains produced a cytotoxic effect on A549 cells, correlating with the amount of tumor necrosis factor alpha (TNF-α) released by the infected monocytes. The addition of TNF-α-neutralizing antibodies to the supernatants from infected monocyte cultures did prevent the induction of a cytotoxic effect on A549 cells overlaid with this mixture but did not prevent the death of epithelial cells when added prior to infection with M. tuberculosis bacilli. Thus, these data agree with previous observations that lung epithelial cells infected with M. tuberculosis bacilli are rapidly killed in vitro. In addition, the data indicate that some of the observed epithelial cell killing may be collateral damage; the result of TNF-α released from M. tuberculosis-infected monocytes.

scholarly journals Virus-Like Particle Vaccine Containing the F Protein of Respiratory Syncytial Virus Confers Protection without Pulmonary Disease by Modulating Specific Subsets of Dendritic Cells and Effector T Cells

2015 ◽  
Vol 89 (22) ◽  
pp. 11692-11705 ◽  
Author(s):  
Ki-Hye Kim ◽  
Young-Tae Lee ◽  
Hye Suk Hwang ◽  
Young-Man Kwon ◽  
Min-Chul Kim ◽  
...  
Keyword(s):  
Weight Loss ◽  
T Cells ◽  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
Immune Correlates ◽  
Virus Like Particle ◽  
Tnf Α ◽  
Ifn Γ ◽  
Syncytial Virus

ABSTRACTThere is no licensed vaccine against respiratory syncytial virus (RSV) since the failure of formalin-inactivated RSV (FI-RSV) due to its vaccine-enhanced disease. We investigated immune correlates conferring protection without causing disease after intranasal immunization with virus-like particle vaccine containing the RSV fusion protein (F VLP) in comparison to FI-RSV and live RSV. Upon RSV challenge, FI-RSV immune mice showed severe weight loss, eosinophilia, and histopathology, and RSV reinfection also caused substantial RSV disease despite their viral clearance. In contrast, F VLP immune mice showed least weight loss and no sign of histopathology and eosinophilia. High levels of interleukin-4-positive (IL-4+) and tumor necrosis factor alpha-positive (TNF-α+) CD4+T cells were found in FI-RSV immune mice, whereas gamma interferon-positive (IFN-γ+) and TNF-α+CD4+T cells were predominantly detected in live RSV-infected mice. More importantly, in contrast to FI-RSV and live RSV that induced higher levels of CD11b+dendritic cells, F VLP immunization induced CD8α+and CD103+dendritic cells, as well as F-specific IFN-γ+and TNF-α+CD8+T cells. These results suggest that F VLP can induce protection without causing pulmonary RSV disease by inducing RSV neutralizing antibodies, as well as modulating specific subsets of dendritic cells and CD8 T cell immunity.IMPORTANCEIt has been a difficult challenge to develop an effective and safe vaccine against respiratory syncytial virus (RSV), a leading cause of respiratory disease. Immune correlates conferring protection but preventing vaccine-enhanced disease remain poorly understood. RSV F virus-like particle (VLP) would be an efficient vaccine platform conferring protection. Here, we investigated the protective immune correlates without causing disease after intranasal immunization with RSV F VLP in comparison to FI-RSV and live RSV. In addition to inducing RSV neutralizing antibodies responsible for clearing lung viral loads, we show that modulation of specific subsets of dendritic cells and CD8 T cells producing T helper type 1 cytokines are important immune correlates conferring protection but not causing vaccine-enhanced disease.

scholarly journals Synergistic Upregulation of Interleukin-8 Secretion from Pulmonary Epithelial Cells by Direct and Monocyte-Dependent Effects of Respiratory Syncytial Virus Infection

2000 ◽  
Vol 74 (18) ◽  
pp. 8425-8433 ◽  
Author(s):  
Lynette H. Thomas ◽  
Melissa I. Y. Wickremasinghe ◽  
Mike Sharland ◽  
Jon S. Friedland
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Interleukin 8 ◽  
Respiratory Epithelial Cells ◽  
Necrosis Factor Alpha ◽  
Leukocyte Influx ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Respiratory Epithelial

ABSTRACT Respiratory syncytial virus (RSV) infection is the major cause of severe bronchiolitis in infants. Pathology of this infection is partly due to excessive proinflammatory leukocyte influx mediated by chemokines. Although direct infection of the respiratory epithelium by RSV may induce chemokine secretion, little is known about the role of cytokine networks. We investigated the effects of conditioned medium (CM) from RSV-infected monocytes (RSV-CM) on respiratory epithelial (A549) cell chemokine release. RSV-CM, but not control CM (both at a 1:5 dilution), stimulated interleukin-8 (IL-8) secretion from A549 cells within 2 h, and secretion increased over 72 h to 11,360 ± 1,090 pg/ml without affecting cell viability. In contrast, RSV-CM had only a small effect on RANTES secretion. RSV-CM interacted with direct RSV infection to synergistically amplify IL-8 secretion from respiratory epithelial cells (levels of secretion at 48 h were as follows: RSV-CM alone, 8,140 ± 2,160 pg/ml; RSV alone, 12,170 ± 300 pg/ml; RSV-CM plus RSV, 27,040 ± 5,260 pg/ml; P < 0.05). RSV-CM induced degradation of IκBα within 5 min but did not affect IκBβ. RSV-CM activated transient nuclear binding of NF-κB within 1 h, while activation of NF-IL6 was delayed until 8 h and was still detectable at 24 h. Promoter-reporter analysis demonstrated that NF-κB binding was essential and that NF-IL6 was important for IL-8 promoter activity in RSV-CM-activated cells. Blocking experiments revealed that the effects of RSV-CM depended on monocyte-derived IL-1 but that tumor necrosis factor alpha was not involved in this network. In summary, RSV infection of monocytes results in and amplifies direct RSV-mediated IL-8 secretion from respiratory epithelial cells by an NF-κB-dependent, NF-IL6-requiring mechanism.

scholarly journals Function of the Respiratory Syncytial Virus Small Hydrophobic Protein

2007 ◽  
Vol 81 (15) ◽  
pp. 8361-8366 ◽  
Author(s):  
Sandra Fuentes ◽  
Kim C. Tran ◽  
Priya Luthra ◽  
Michael N. Teng ◽  
Biao He
Keyword(s):  
Respiratory Syncytial Virus ◽  
Tumor Necrosis ◽  
Parainfluenza Virus ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Small Hydrophobic Protein ◽  
Factor Alpha ◽  
Syncytial Virus ◽  
Small Hydrophobic ◽  
Necrosis Factor

ABSTRACT Respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, encodes a small hydrophobic (SH) protein of unknown function. Parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, also encodes an SH protein, which inhibits tumor necrosis factor alpha (TNF-α) signaling. In this study, recombinant PIV5 viruses without their own SH but containing RSV SH (from RSV strain A2 or B1) in its place (PIV5ΔSH-RSV SH) and RSV lacking its own SH (RSVΔSH) were generated and analyzed. The results indicate that the SH protein of RSV has a function similar to that of PIV5 SH and that it can inhibit TNF-α signaling.

scholarly journals RNA Interference-Mediated Silencing of the Respiratory Syncytial Virus Nucleocapsid Defines a Potent Antiviral Strategy

2009 ◽  
Vol 53 (9) ◽  
pp. 3952-3962 ◽  
Author(s):  
Rene Alvarez ◽  
Sayda Elbashir ◽  
Todd Borland ◽  
Ivanka Toudjarska ◽  
Philipp Hadwiger ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Rna Interference ◽  
Antiviral Agent ◽  
Necrosis Factor Alpha ◽  
Nucleocapsid Gene ◽  
Antiviral Efficacy ◽  
Syncytial Virus ◽  
Rapid Amplification

ABSTRACT We describe the design and characterization of a potent human respiratory syncytial virus (RSV) nucleocapsid gene-specific small interfering RNA (siRNA), ALN-RSV01. In in vitro RSV plaque assays, ALN-RSV01 showed a 50% inhibitory concentration of 0.7 nM. Sequence analysis of primary isolates of RSV showed that the siRNA target site was absolutely conserved in 89/95 isolates, and ALN-RSV01 demonstrated activity against all isolates, including those with single-mismatch mutations. In vivo, intranasal dosing of ALN-RSV01 in a BALB/c mouse model resulted in potent antiviral efficacy, with 2.5- to 3.0-log-unit reductions in RSV lung concentrations being achieved when ALN-RSV01 was administered prophylactically or therapeutically in both single-dose and multidose regimens. The specificity of ALN-RSV01 was demonstrated in vivo by using mismatch controls; and the absence of an immune stimulatory mechanism was demonstrated by showing that nonspecific siRNAs that induce alpha interferon and tumor necrosis factor alpha lack antiviral efficacy, while a chemically modified form of ALN-RSV01 lacking measurable immunostimulatory capacity retained full activity in vivo. Furthermore, an RNA interference mechanism of action was demonstrated by the capture of the site-specific cleavage product of the RSV mRNA via rapid amplification of cDNA ends both in vitro and in vivo. These studies lay a solid foundation for the further investigation of ALN-RSV01 as a novel therapeutic antiviral agent for clinical use by humans.

scholarly journals Inhibitory Effect of Sargassum fusiforme and Its Components on Replication of Respiratory Syncytial Virus In Vitro and In Vivo

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 548
Author(s):  
Kiramage Chathuranga ◽  
Asela Weerawardhana ◽  
Niranjan Dodantenna ◽  
Lakmal Ranathunga ◽  
Won-Kyung Cho ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Agent ◽  
Active Components ◽  
Sargassum Fusiforme ◽  
Antiviral Effects ◽  
Improve Life Expectancy ◽  
Rsv Infection ◽  
Syncytial Virus

Sargassum fusiforme, a plant used as a medicine and food, is regarded as a marine vegetable and health supplement to improve life expectancy. Here, we demonstrate that S. fusiforme extract (SFE) has antiviral effects against respiratory syncytial virus (RSV) in vitro and in vivo mouse model. Treatment of HEp2 cells with a non-cytotoxic concentration of SFE significantly reduced RSV replication, RSV-induced cell death, RSV gene transcription, RSV protein synthesis, and syncytium formation. Moreover, oral inoculation of SFE significantly improved RSV clearance from the lungs of BALB/c mice. Interestingly, the phenolic compounds eicosane, docosane, and tetracosane were identified as active components of SFE. Treatment with a non-cytotoxic concentration of these three components elicited similar antiviral effects against RSV infection as SFE in vitro. Together, these results suggest that SFE and its potential components are a promising natural antiviral agent candidate against RSV infection.

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