Ergosterol peroxide suppresses influenza A virus-induced pro-inflammatory response and apoptosis by blocking RIG-I signaling

Zhou, Beixian; Liang, Xiaoli; Feng, Qitong; Li, Jing; Pan, Xiping; Xie, Peifang; Jiang, Zhi‐Hong; Yang, Zifeng

doi:10.1016/j.ejphar.2019.172543

Cited by 19 publications

(14 citation statements)

References 55 publications

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“…Some anti-viral compounds could reduce the expression levels of inflammatory factors (IL-1, IL-6, and TNF-α, etc.) by suppressing the activation of RIG-I and TLR3 [54][55][56]. Consistent with these findings, our study showed that 3D administration could repress the expression of inflammatory cytokines (IL-6, IL-8, IL-1β, and TNF-α) by inhibiting RIG-I, TLR3, and their downstream signal factors (TLR7, MAVS, Myd88, etc.)…”

Section: Discussionsupporting

confidence: 89%

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

Wang

Fang

Luo

et al. 2021

Viruses

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Influenza A virus is a highly variable and contagious respiratory pathogen that can cause annual epidemics and it poses an enormous threat to public health. Therefore, there is an urgent need for a new generation of antiviral drugs to combat the emergence of drug-resistant strains of the influenza virus. A novel series of butene lactone derivatives were screened and the compound 3D was selected, as it exhibited in vitro potential antiviral activity against A/Weiss/43 H1N1 virus with low toxicity. In addition, 3D dose-dependently inhibited the viral replication, expression of viral mRNA and viral proteins. 3D exerted a suppressive effect on A/Virginia/ATCC2/2009 H1N1 and A/California/2/2014 H3N2 in vitro. The time-of-addition analysis indicated that 3D suppressed H1N1 in the early stage of its life cycle. A/Weiss/43 H1N1-induced apoptosis in A549 cells was reduced by 3D via the mitochondrial apoptosis pathway. 3D could decrease the production of H1N1-induced pro-inflammatory cytokines that are induced by H1N1 in vitro and in vivo. The administration of 3D reduced lung lesions and virus load in vivo. These results suggest that 3D, which is a butene lactone derivative, is a promising agent for the treatment of influenza A virus infection.

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Section: Discussionsupporting

confidence: 89%

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

Wang

Fang

Luo

et al. 2021

Viruses

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“…As we know, IFN-γ as well as IFN-α/β plays crucial role in antiviral defense (Zhou et al, 2019). On the contrary, they were also implicated in exacerbating inflammation and worsening the outcomes of infectious diseases including IAV infection (Zhou et al, 2019). Similarly, the role of Gal-1 in reducing IFN-γ expression was also reported in EBV and HSV infections and reduced tissue injuries (Gandhi et al, 2007;Rajasagi et al, 2012), these researches also partly support our results.…”

Section: Discussionsupporting

confidence: 85%

“…Notably, we found decreased levels of IFN-γ in both serum and BALF after Gal-1 treatment although the difference was not significant. As we know, IFN-γ as well as IFN-α/β plays crucial role in antiviral defense (Zhou et al, 2019). On the contrary, they were also implicated in exacerbating inflammation and worsening the outcomes of infectious diseases including IAV infection (Zhou et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 Ameliorates Influenza A H1N1pdm09 Virus-Induced Acute Lung Injury

et al. 2020

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Influenza remains one of the major epidemic diseases worldwide. Acute lung injury mainly caused by excessive pro-inflammatory host immune responses leads to high mortality rates in severe influenza patients. Galectin-1, an animal lectin ubiquitously expressed in mammalian tissues, is reported to play important roles in viral diseases. Here, we established murine and A549 cell models to explore the potential roles of galectin-1 treatment in H1N1pdm09-induced acute lung injury. We found that galectin-1 protein level was elevated in A549 cell culture supernatants and mouse BALF after H1N1pdm09 challenge. In vivo experiments showed recombinant galectin-1 treatment reduced wet/dry weight ratio, inflammatory cell infiltration in mouse lungs and mediated the expression of cytokines and chemokines including IL-1β, IL-6, IL-10, IL-12(p40), IL-12(p70), G-CSF, MCP-1, MIP-1α and RANTES in serum and BALF of infected mice. Reduced apoptosis and viral titers in mouse lungs were also found after galectin-1 treatment. As expected, galectin-1 treated mice performed reduced body weight loss and enhanced survival rate against H1N1pdm09 challenge. In addition, in vitro experiments showed that viral titers decreased in a dose-dependent manner and cell apoptosis in A549 cells reduced after recombinant galectin-1 treatment. Taken together, our findings indicate a potentially positive effect of Gal-1 treatment on ameliorating the progress of H1N1pdm09-induced acute lung injury and recombinant galectin-1 might serve as a new agent in treating influenza.

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“…The cytotoxicity of sinensetin on A549 cells was evaluated by MTT assay as described previously [34]. Briefly, A549 cells were cultivated into 96-well plates at a density of 5 × 10 4 cells per well for 12 h incubation, allowing cells to adhere.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Xiang

Liang

et al. 2020

BMC Complement Med Ther

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Background: Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the antiinflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations.Methods: The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virustriggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot. Results: Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E 2 (PGE 2 ) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings.Conclusion: Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics.

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Ergosterol peroxide suppresses influenza A virus-induced pro-inflammatory response and apoptosis by blocking RIG-I signaling

Cited by 19 publications

References 55 publications

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

Galectin-1 Ameliorates Influenza A H1N1pdm09 Virus-Induced Acute Lung Injury

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

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