stilbenes and Respiratory-Syncytial-Virus-Infections

Respiratory syncytial virus (RSV) infection is involved in persistent and recurrent wheezing. There are no effective and safe drugs for the sequelae of persistent wheezing after early bronchiolitis. In this study, we investigated the effect of resveratrol on persistent airway inflammation and airway hyperresponsiveness (AHR) induced by RSV infection. RSV-infected mice were sacrificed at serial time points after infection to collect samples and measure the number of inflammatory cells and levels of interferon-gamma (IFN-γ), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). Airway inflammation, AHR, and the levels of NGF and BDNF were detected after resveratrol administration. Furthermore, Ab-NGF was used to investigate the role of NGF in RSV-induced prolonged airway inflammation and AHR. We found that RSV RNA remained detectable in the lungs of RSV-infected mice on day 60, accompanying persistent airway inflammation and AHR for 60 days. IFN-γ levels in BALF were increased on day 7 but reduced to normal levels by day 14 post-RSV infection, while NGF and BDNF levels gradually increased from day 14 to 60. Furthermore, after resveratrol treatment, the total number of cells in BALF was reduced; the number of inflammatory cells infiltrating the lungs was also lower. Resveratrol attenuated the airway response to methacholine and significantly decreased NGF levels in BALF without affecting BDNF levels. Moreover, airway inflammation and AHR associated with RSV persistence were attenuated after Ab-NGF administration. In all, resveratrol suppresses persistent airway inflammation and AHR might partially through reducing the levels of NGF after RSV infection.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain-Derived Neurotrophic Factor; Bronchoalveolar Lavage Fluid; Female; Interferon-gamma; Lung; Mice; Mice, Inbred BALB C; Nerve Growth Factor; Pneumonia; Respiratory Function Tests; Respiratory Hypersensitivity; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Resveratrol; RNA, Viral; Stilbenes

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in young children and the leading cause of infant hospitalization worldwide. Uncontrolled response to RSV is mediated by a toll-like receptor (TLR)-mediated immune response. Resveratrol possesses anti-RSV activity and is an inhibitor of the TRIF/TBK1/IRF-3 complex. We hypothesize that resveratrol inhibits the TRIF-dependent pathway through upregulation of SARM post-RSV infection. BALB/c mice were infected with RSV and were injected with resveratrol 1 h postinoculation. SARM short interfering RNA was administered to RSV-infected and resveratrol-treated mice. Lung function was measured by whole-body plethysmography, lung histopathology was examined, and lymphocytes in bronchoalveolar lavage fluid were quantified. SARM and TRIF protein expression were detected in the lung by Western blot analyses. The expression of gamma interferon in bronchoalveolar lavage fluid (BALF) was evaluated by enzyme-linked immunosorbent assay (ELISA). SARM expression was reduced and TRIF expression was increased after infection with RSV. Resveratrol increased SARM expression and decreased TRIF expression after RSV infection. SARM knockdown in resveratrol-treated mice enhanced gamma interferon production, RSV-induced airway inflammation, and airway hyperresponsiveness (AHR). Resveratrol decreased TRIF expression and prevented the RSV-mediated reduction of SARM expression. Resveratrol-mediated inhibition of the TRIF-dependent pathway may be dependent on SARM expression.. Our study provides insights into the regulation of innate immunity in response to RSV infection. The results suggest that resveratrol-mediated alterations in SARM have therapeutic potential against RSV immunopathology caused by deregulation of the TLR-mediated immune response. Ultimately, improved insight into the complex interplay between TLR adaptor proteins and the occurrence of severe RSV infection might lead to novel therapeutic treatment strategies, such as TLR adjuvants.

Topics: Adaptor Proteins, Vesicular Transport; Animals; Armadillo Domain Proteins; Cytoskeletal Proteins; Down-Regulation; Female; Humans; Lung; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Resveratrol; Signal Transduction; Stilbenes; Up-Regulation

Explore the influence of baicalin joint resveratrol retention enema on TNF-α, SIgA, IL-2, and IFN-γ of rats with respiratory syncytial virus (RSV) infection. The 60 SD rats were randomly divided into normal group, model group, baicalin group, resveratrol group, joint group, and ribavirin group. For model group, baicalin group, resveratrol group, joint group, and ribavirin group, rats were given RSV virus suspension intranasally for 3 days, and model group was not given administration. Baicalin group, resveratrol group, joint group, and ribavirin group were, respectively, given baicalin 100 mg/kg/day, resveratrol 30 mg/kg/day, baicalin joint resveratrol, and ribavirin 1 g/kg/day retention enema. After continuously given administration 7 days, rats were measured in serum TNF-α, IL-2, IFN-γ levels and SIgA levels in bronchoalveolar lavage fluid. Model group, TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than the normal group (P < 0.05); Baicalin group, resveratrol group, ribavirin group, TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than the model group (P < 0.05); TNF-α, IL-2 between baicalin group, resveratrol group, ribavirin group, have no significant difference (P > 0.05); Baicalin group, resveratrol group, joint group, IFN-γ, and SIgA were significantly higher than the ribavirin group (P < 0.05); Joint group TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than baicalin group, resveratrol group, and ribavirin group (P < 0.05). Baicalin joint resveratrol retention enema can increase RSV infection model in rats serum TNF-α, IL-2, IFN-γ levels and SIgA levels in bronchoalveolar lavage fluid, which may anti-virus through this mechanism.

Topics: Animals; Antiviral Agents; Cell Line; Drug Interactions; Enema; Female; Flavonoids; Humans; Immunoglobulin A, Secretory; Interferon-gamma; Interleukin-2; Male; Rats; Rats, Sprague-Dawley; Respiratory Syncytial Virus Infections; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

Respiratory syncytial virus (RSV) is the most common pathogen responsible for lower respiratory diseases in children. So far, there is no effective treatment or preventative vaccine available for RSV infection, although ribavirin and dexamethasone are commonly prescribed. Resveratrol has been shown to inhibit the replication of several other viruses, thus the effect of resveratrol on RSV-induced inflammatory mediators in 9HTEo cell cultures was evaluated, and possible mechanisms of action were explored and compared with dexamethasone and ribavirin. Incubation with resveratrol resulted in decreased IL-6 production and partial inhibition of RSV replication. Resveratrol treatment also inhibited virus-induced TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK binding kinase 1 (TBK1) protein expression. These data demonstrate the ability of resveratrol to inhibit cytokine production by RSV in airway epithelial cells, indicating that it might be a therapeutic agent with both anti-inflammatory and antiviral potential for the treatment of RSV infection.

Topics: Adaptor Proteins, Vesicular Transport; Antiviral Agents; Cell Line; Dexamethasone; Down-Regulation; Epithelial Cells; Humans; Interleukin-6; Interleukin-8; Protein Serine-Threonine Kinases; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory System; Resveratrol; Ribavirin; Stilbenes; Virus Replication

Glomerular podocytes are highly specialized epithelial cells whose injury in glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an early event in podocyte injury, we tested whether a major regulator of oxidative metabolism and mitochondrial function, the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), affects podocyte damage. Aldosterone-induced injury decreased PGC-1α expression, and induced mitochondrial and podocyte damage in dose- and time-dependent manners. The suppression of endogenous PGC-1α by RNAi caused podocyte mitochondrial damage and apoptosis while its increase by infection with an adenoviral vector prevented aldosterone-induced mitochondrial malfunction and inhibited injury. Overexpression of the silent mating type information regulation 2 homolog 1, a gene upstream of PGC-1α, prevented aldosterone-induced mitochondrial damage and podocyte injury by upregulating PGC-1α at both the transcriptional and post-translational levels. Resveratrol, a SIRT1 activator, attenuated aldosterone-induced mitochondrial malfunction and podocyte injury in vitro and in aldosterone-infused mice in vivo. Hence, endogenous PGC-1α may be important for maintenance of mitochondrial function in podocytes under normal conditions. Activators of SIRT1, such as resveratol, may be therapeutically useful in glomerular diseases to promote and maintain PGC-1α expression and, consequently, podocyte integrity.

Topics: Aldosterone; Animals; Apoptosis; Cell Line; Cytoprotection; Disease Models, Animal; Enzyme Activation; Gene Expression Regulation; Genes, Reporter; Kidney Diseases; Mice; Mice, Inbred C57BL; Mineralocorticoid Receptor Antagonists; Mitochondria; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Podocytes; Promoter Regions, Genetic; Receptors, Mineralocorticoid; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Resveratrol; RNA Interference; Sirtuin 1; Stilbenes; Time Factors; Trans-Activators; Transcription Factors; Transfection

To study the regulation trend of resveratrol on TNF-alpha, IL-1beta, IL-6 expressions in bronchoalveolar layage fluid (BALF) of RSV-infected BALB/c mice at different time points.. RSV-induced BALB/c mice were orally administered with resveratrol. Their BALFs were collected at 24, 72 and 144 h after the first nasal drip with RSV to detect the level of TNF-alpha, IL-1P3, IL-6 by EILSA.. The expression of TNF-alpha, IL-1Pf and IL-6 in BALF increased significantly compared with the normal group (P <0. 01) after 24 hours of RSV infection, while the expression of TNF-alpha (P < 0.01), IL-1beta (P < 0.05), IL-6 (P < 0.01) in the resveratrol group decreased notably compared with the model group. After 72 hours of infection with RSV, although the expression of TNF-alpha (P < 0.05), IL-1beta (P < 0.01) and IL-6 (P < 0.01) in BALF in model group were higher than those in the normal group, they were much more lower than at 24 h. The expression of IL-1beta and IL-6 (P < 0.05) in the resveratrol groups were down-regulated significantly, but no difference had been shown in TNF-alpha expression compared with the RSV infection group. After infection with RSV for 144 h, the expression of IL-1beta (P < 0.01) and IL-6 (P < 0.05) in BALF in the model group were higher than those in the normal group, but there was no difference in the secretion of TNF-alpha. The expression of TNF-alpha, IL-1beta and IL-6 showed also no remarkable difference between the resveratrol groups and the RSV infection group.. Resveratrol can inhibit the over expression of inflammatory factors TNF-alpha, IL-1beta, IL-6 in bronchoalveolar lavage fluid of RSV-induced BALB/c mice and keep them at a low level with the passing of infection time.

Topics: Animals; Bronchoalveolar Lavage Fluid; Female; Interleukin-1beta; Interleukin-6; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus Infections; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

Respiratory syncytial virus (RSV) is the most important cause of severe, lower respiratory tract infections in infants, and RSV infections have been associated with chronic wheezing and asthma during childhood. However, the mechanism of RSV-induced airway inflammation and airway hyperresponsiveness (AHR) is poorly understood. Furthermore, there are presently neither effective vaccines nor drugs available for the prevention or treatment of RSV infections. In this study, we investigated the effect of the plant extract resveratrol as a means of preventing airway inflammation and attenuating RSV-induced AHR. Our data showed that resveratrol reduced RSV lung titers and the number of infiltrating lymphocytes present in bronchoalveolar lavage fluid (BALF) and reduced inflammation. Furthermore, resveratrol attenuated airway responses to methacholine following RSV infection and significantly decreased gamma interferon (IFN-γ) levels in BALF of RSV-infected mice. Data presented in this report demonstrated that resveratrol controlled Toll-like receptor 3 (TLR3) expression, inhibited the TRIF signaling pathway, and induced M2 receptor expression following RSV infection. These data support a role for the use of resveratrol as a means of reducing IFN-γ levels associated with RSV-mediated airway inflammation and AHR, which may be mediated via TLR3 signaling.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchoalveolar Lavage Fluid; Female; Gene Expression Profiling; Inflammation; Interferon-gamma; Lung; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Resveratrol; Signal Transduction; Stilbenes; Toll-Like Receptor 3; Viral Load