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Targeting the pro-inflammatory factor CCL2 (MCP-1) with Bindarit for influenza A (H7N9) treatment

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ABSTRACT

Influenza A viruses are important human and animal pathogens. Seasonal influenza viruses cause infections every year, and occasionally zoonotic viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. Three cases of laboratory confirmed human infection with avian influenza A (H7N9) virus were reported in 2013, and there have been several cases reported across South East Asia, and recently in North America. Most patients experience severe respiratory illness, with mortality rates approaching 40%. No vaccine is currently available and the use of antivirals is complicated due to the emergence of drug resistant strains. Thus, there is a need to identify new drugs for therapeutic intervention and disease control. In humans, following H7N9 infection, there is excessive expression of pro-inflammatory factors CCL2, IL-6, IL-8, IFNα, interferon-γ, IP-10, MIG and macrophage inflammatory protein-1β, which has been shown to contribute to fatal disease outcomes in mouse models of infection. In the current study, the potent inhibitor of CCL2 synthesis, Bindarit, was examined as a countermeasure for H7N9-induced inflammation in a mouse model. Bindarit treatment of mice did not have any substantial therapeutic efficacy in H7N9 infection. Consequently, the results suggest that Bindarit may be ill-advised in the treatment of influenza H7N9 infection.

No MeSH data available.


Bindarit reduces CCL2 gene expression in IAV-infected cells. A549 cells were infected with A/Ca (H1N1) at MOI 0.1 and subsequently treated with Bindarit at 100 μm. At 24 h pi, RNA was extracted for host gene expression analysis of CCL2 using RT-qPCR. Expression was normalized to 18 s and compared to non-infected cells. Data are from two independent experiments using three replicates per group.
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fig1: Bindarit reduces CCL2 gene expression in IAV-infected cells. A549 cells were infected with A/Ca (H1N1) at MOI 0.1 and subsequently treated with Bindarit at 100 μm. At 24 h pi, RNA was extracted for host gene expression analysis of CCL2 using RT-qPCR. Expression was normalized to 18 s and compared to non-infected cells. Data are from two independent experiments using three replicates per group.

Mentions: To evaluate the effectiveness of Bindarit in reducing CCL2 production, lung epithelial cells were infected (MOI=0.1) with A/California/04/09 (A/Ca; H1N1) virus and simultaneously treated with Bindarit. Quantitative reverse transcription PCR (RT-qPCR) was used to investigate the effect of Bindarit on CCL2 gene expression during infection with A/Ca (H1N1), a representative, currently circulating IAV subtype, in a human epithelial cell (A549) line. CCL2 was considerably upregulated by 3.21-fold (P<0.01) in A/Ca (H1N1)-infected A549 cells compared to mock-infected controls at 24 h pi (Figure 1). When A549 cells were treated with Bindarit (100 μm), CCL2 gene expression was significantly (P<0.01) reduced to a level comparable to mock-infected controls.


Targeting the pro-inflammatory factor CCL2 (MCP-1) with Bindarit for influenza A (H7N9) treatment
Bindarit reduces CCL2 gene expression in IAV-infected cells. A549 cells were infected with A/Ca (H1N1) at MOI 0.1 and subsequently treated with Bindarit at 100 μm. At 24 h pi, RNA was extracted for host gene expression analysis of CCL2 using RT-qPCR. Expression was normalized to 18 s and compared to non-infected cells. Data are from two independent experiments using three replicates per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382437&req=5

fig1: Bindarit reduces CCL2 gene expression in IAV-infected cells. A549 cells were infected with A/Ca (H1N1) at MOI 0.1 and subsequently treated with Bindarit at 100 μm. At 24 h pi, RNA was extracted for host gene expression analysis of CCL2 using RT-qPCR. Expression was normalized to 18 s and compared to non-infected cells. Data are from two independent experiments using three replicates per group.
Mentions: To evaluate the effectiveness of Bindarit in reducing CCL2 production, lung epithelial cells were infected (MOI=0.1) with A/California/04/09 (A/Ca; H1N1) virus and simultaneously treated with Bindarit. Quantitative reverse transcription PCR (RT-qPCR) was used to investigate the effect of Bindarit on CCL2 gene expression during infection with A/Ca (H1N1), a representative, currently circulating IAV subtype, in a human epithelial cell (A549) line. CCL2 was considerably upregulated by 3.21-fold (P<0.01) in A/Ca (H1N1)-infected A549 cells compared to mock-infected controls at 24 h pi (Figure 1). When A549 cells were treated with Bindarit (100 μm), CCL2 gene expression was significantly (P<0.01) reduced to a level comparable to mock-infected controls.

View Article: PubMed Central - PubMed

ABSTRACT

Influenza A viruses are important human and animal pathogens. Seasonal influenza viruses cause infections every year, and occasionally zoonotic viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. Three cases of laboratory confirmed human infection with avian influenza A (H7N9) virus were reported in 2013, and there have been several cases reported across South East Asia, and recently in North America. Most patients experience severe respiratory illness, with mortality rates approaching 40%. No vaccine is currently available and the use of antivirals is complicated due to the emergence of drug resistant strains. Thus, there is a need to identify new drugs for therapeutic intervention and disease control. In humans, following H7N9 infection, there is excessive expression of pro-inflammatory factors CCL2, IL-6, IL-8, IFN&alpha;, interferon-&gamma;, IP-10, MIG and macrophage inflammatory protein-1&beta;, which has been shown to contribute to fatal disease outcomes in mouse models of infection. In the current study, the potent inhibitor of CCL2 synthesis, Bindarit, was examined as a countermeasure for H7N9-induced inflammation in a mouse model. Bindarit treatment of mice did not have any substantial therapeutic efficacy in H7N9 infection. Consequently, the results suggest that Bindarit may be ill-advised in the treatment of influenza H7N9 infection.

No MeSH data available.