Forsythoside A Inhibits BVDV Replication via TRAF2-Dependent CD28–4-1BB Signaling in Bovine PBMCs

Song, Quanjiang; Weng, Xiaogang; Cai, Dongjie; Zhang, Wang; Wang, Jiufeng

doi:10.1371/journal.pone.0162791

Cited by 17 publications

(11 citation statements)

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“…For example, Fa inhibited cell apoptosis by reducing levels of caspase-9 by 40% and caspase-3 by 53% in an androgenic alopecia mouse model (25). Song et al (26) observed that Fa effectively inhibited the replication of bovine viral diarrhea virus, as well as apoptosis induced by bovine viral diarrhea virus in bovine peripheral blood mononuclear cells (26). Similarly, in the present study, cell apoptosis was markedly inhibited by Fa treatment, and its function was accompanied by the reduced expression levels of caspase-3 and caspase-9.…”

Section: Discussionmentioning

confidence: 99%

Forsythiaside A protects against focal cerebral ischemic injury by mediating the activation of the Nrf2 and endoplasmic reticulum stress pathways

Shi

Wang

2019

Mol Med Report

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ischemic stroke is a common type of stroke with a high mortality and morbidity rate. Preventing and controlling cerebral ischemic injury is particularly important. Forsythiaside A (FA) has been reported to have anti-inflammatory and antioxidant activities. The aim of the present study was to explore the impact of Fa on middle cerebral artery occlusion (Mcao)-induced cerebral ischemic injury in rats. The results indicated that Fa markedly increased the percent survival and decreased the neurological deficit score in rats with cerebral ischemic injury. Furthermore, cell apoptosis was significantly inhibited by Fa administration, which was accompanied by decreased caspase-3 and caspase-9 expression. a marked increase in the expression levels of nuclear factor-erythroid 2-related factor 2 (nrf2), nad(P)H quinone dehydrogenase 1 and glutathione-s-transferase was detected in Fa-treated rats. in addition, treatment with Fa reduced malonaldehyde expression, and enhanced the expression of superoxide dismutase and glutathione. Furthermore, endoplasmic reticulum (er) stress was vastly alleviated by Fa treatment, as evidenced by the increased expression of B-cell lymphoma 2, apoptosis regulator and the downregulated expression of phosphorylated (phospho)-protein kinase rna-like er kinase (PerK)/PerK, phospho-inositol-requiring enzyme 1 (ire1α)/ire1α and ccaaT-enhancer-binding proteins homologous protein.Taken together, the present study demonstrated that Fa attenuated cerebral ischemic damage via mediation of the activation of nrf2 and er stress pathways. These data may provide ideas for novel treatment strategies of cerebral ischemic damage.

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Section: Discussionmentioning

confidence: 99%

Forsythiaside A protects against focal cerebral ischemic injury by mediating the activation of the Nrf2 and endoplasmic reticulum stress pathways

Shi

Wang

2019

Mol Med Report

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“…Peripheral blood mononuclear cells (PBMCs), including lymphocytes, monocytes and macrophages, play a pivotal role in the host innate or adaptive immune responses to viral infection. PBMCs were the main target of BVDV infection, infection of lymphocytes and monocytes by BVDV resulted in lymphoid depletion of B cells, T helper cells, cytotoxic T cells and γ-δ T cells [20, 21]. PBMCs have been proved to be a suitable model for characterizing the host immune responses to virus infection and have been utilized for the evaluation of immune responses to animal viruses [17, 22, 23].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis reveals differential immune related genes expression in bovine viral diarrhea virus-2 infected goat peripheral blood mononuclear cells (PBMCs)

Shu

et al. 2019

BMC Genomics

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Background Bovine viral diarrhea virus (BVDV) is an economically important viral pathogen of domestic and wild ruminants. Apart from cattle, small ruminants (goats and sheep) are also the susceptible hosts for BVDV. BVDV infection could interfere both of the innate and adaptive immunity of the host, while the genes and mechanisms responsible for these effects have not yet been fully understood. Peripheral blood mononuclear cells (PBMCs) play a pivotal role in the immune responses to viral infection, and these cells were the target of BVDV infection. In the present study, the transcriptome of goat peripheral blood mononuclear cells (PBMCs) infected with BVDV-2 was explored by using RNA-Seq technology. Results Goat PBMCs were successfully infected by BVDV-2, as determined by RT-PCR and quantitative real-time RT-PCR (qRT-PCR). RNA-Seq analysis results at 12 h post-infection (hpi) revealed 499 differentially expressed genes (DEGs, fold-change ≥ ± 2, p < 0.05) between infected and mock-infected PBMCs. Of these genes, 97 were up-regulated and the remaining 352 genes were down-regulated. The identified DEGs were found to be significantly enriched for locomotion/ localization, immune response, inflammatory response, defense response, regulation of cytokine production, etc., under GO enrichment analysis. Cytokine-cytokine receptor interaction, TNF signaling pathway, chemokine signaling pathway, etc., were found to be significantly enriched in KEGG pathway database. Protein-protein interaction (PPI) network analysis indicated most of the DEGs related to innate or adaptive immune responses, inflammatory response, and cytokine/chemokine-mediated signaling pathway. TNF, IL-6, IL-10, IL-12B, GM-CSF, ICAM1, EDN1, CCL5, CCL20, CXCL10, CCL2, MAPK11, MAPK13, CSF1R and LRRK1 were located in the core of the network and highly connected with other DGEs. Conclusions BVDV-2 infection of goat PBMCs causes the transcription changes of a series of DEGs related to host immune responses, including inflammation, defense response, cell locomotion, cytokine/chemokine-mediated signaling, etc. The results will be useful for exploring and further understanding the host responses to BVDV-2 infection in goats. Electronic supplementary material The online version of this article (10.1186/s12864-019-5830-y) contains supplementary material, which is available to authorized users.

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“…In initial studies, Forsythoside A (2-(3,4-Dihydroxyphenyl)ethyl 6-O-(6-deoxy-β-D-gulopyranosyl)-4-O-[(2E)-3-(3,4-dihydroxyphenyl)-2-propenoyl]-α-L-altropyranoside) was also evaluated as a potential compound to eliminate the persistent BVDV infection using an approach similar to that described by Song et al ( 21 ). However, experiments were stopped after the second passage, given that Forsythoside A used at 100 μg/mL in DMEM + BS inhibited LFBK-α v β 6 cell growth.…”

Section: Discussionmentioning

confidence: 99%

Elimination of Non-cytopathic Bovine Viral Diarrhea Virus From the LFBK-αvβ6 Cell Line

et al. 2021

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The LFBK-αvβ6 cell line is highly sensitive for the isolation of foot-and-mouth disease virus (FMDV) and porcinophilic vesicular viruses. However, LFBK-αvβ6 cells are contaminated with a non-cytopathic bovine viral diarrhea virus (BVDV), which complicates handling procedures in areas where other cell lines are maintained, as well downstream use of viral isolates. In this study, we used an aromatic cationic compound (DB772) to treat LFBK-αvβ6 cells using an approach that has been previously used to eliminate persistent BVDV from fetal fibroblast cell lines. After three cell passages with 4 μM DB772, BVDV could no longer be detected in unclarified cell suspensions using a pan-pestivirus real-time RT-PCR assay, and remained undetectable after treatment was stopped (nine passages) for an additional 28 passages. The analytical sensitivity of the DB772-treated LFBK-αvβ6 cultures (renamed WRL-LFBK-αvβ6) to titrations of FMDV and other vesicular virus isolates was comparable to untreated LFBK-αvβ6 cells. These new BVDV-free cells can be handled without the risk of cross-contaminating other cells lines or reagents, and used for routine diagnostics, in vivo studies and/or preparation of new vaccine strains.

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Forsythoside A Inhibits BVDV Replication via TRAF2-Dependent CD28–4-1BB Signaling in Bovine PBMCs

Cited by 17 publications

References 64 publications

Forsythiaside A protects against focal cerebral ischemic injury by mediating the activation of the Nrf2 and endoplasmic reticulum stress pathways

Forsythiaside A protects against focal cerebral ischemic injury by mediating the activation of the Nrf2 and endoplasmic reticulum stress pathways

Transcriptome analysis reveals differential immune related genes expression in bovine viral diarrhea virus-2 infected goat peripheral blood mononuclear cells (PBMCs)

Elimination of Non-cytopathic Bovine Viral Diarrhea Virus From the LFBK-αvβ6 Cell Line

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