RESUMO
In order to better understand the early pathways of the pathogenesis of, and immune response to, RSV, herein, we explored the relationship between TLR7 expression and oxidative stress induction following RSV infection in A549 cells. We studied the intervening effects of the Nrf2/ARE pathway agonist butylated hydroxyanisole (BHA) and inhibitor trigonelline (TRI) on TLR7 modulation or oxidative stress induction. For comparison purposes, we set up seven treatment groups in this study, including RSV-treated cells, BHA + RSV-treated cells, TRI + RSV-treated cells, normal cell controls, inactivated RSV controls, BHA controls and TRI controls. We measured changes in TLR7, IL-6, TNF-α mRNA using RT-PCR and IL-6, TNF-α and IL-1ß protein using ELISA as well as TLR7, Nrf2 and HO-1 protein using Western blot in A549 cells from the different treatment groups. We also assessed changes in cell proliferation and measured changes in ·OH and NO in A549 cells from the different treatment groups. The results indicate that TLR7 up-regulation is related to RSV infection and the induction of oxidative stress and that TLR7 expression was mediated by the anti-inflammatory effects of Nrf2/ARE pathway inhibitors or agonists. Our experiments may help elucidate the underlying pathology of RSV infection and suggest potential therapeutic targets for drug development and the prevention of RSV-induced human diseases.
Assuntos
Células Epiteliais Alveolares/virologia , Elementos de Resposta Antioxidante , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Vírus Sincicial Respiratório Humano/imunologia , Receptor 7 Toll-Like/genética , Células A549 , Alcaloides/farmacologia , Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/metabolismo , Hidroxianisol Butilado/farmacologia , Proliferação de Células , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Receptor 7 Toll-Like/biossíntese , Receptor 7 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Regulação para CimaRESUMO
Respiratory syncytial virus (RSV) is the key underlying cause of acute lower respiratory tract infection in infants; however, no licensed vaccine against RSV infection is currently available. This study was undertaken to assess the preventive effect of vaccine on RSV infection. In this metaanalysis, 1,792 published randomized clinical trials of RSV vaccines from Jan 1973 to Sep 2015 were examined. Among thirteen studies that met the inclusion criteria, eleven studies estimated the impact of RSV vaccines and four studies estimated the effect of adjuvants. The odds ratios (ORs) were 0.31 (95% CI, 0.15-0.67) and 0.62 (95% CI, 0.29-1.34), respectively. We found that RSV subunit vaccines can significantly reduce the incidence of RSV infection and that whether vaccination with adjuvant therapy was an effective strategy still remained to be studied. This analysis of the preventive effect of vaccines on RSV infection has direct applications for the prevention of RSV infections.
