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

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, 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.


Related in: MedlinePlus

Effect of Bindarit on protein level of pro-inflammatory following avian IAV H7N9 infection. Mice were infected i.n. with a sub-lethal dose of A/Anhui (H7N9) or PBS. Mice were then treated with either Bindarit or vehicle starting at day 1 pi. On day 8 pi, mice were killed and BAL was collected for protein expression analysis of CCL2 (a), IL-6 (b), RANTES (c), IL-15 (d) and TNFα (e) with a multiplex enzyme-linked immunosorbent assay. Data are from five mice per group±s.e.m. *P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5382437&req=5

fig7: Effect of Bindarit on protein level of pro-inflammatory following avian IAV H7N9 infection. Mice were infected i.n. with a sub-lethal dose of A/Anhui (H7N9) or PBS. Mice were then treated with either Bindarit or vehicle starting at day 1 pi. On day 8 pi, mice were killed and BAL was collected for protein expression analysis of CCL2 (a), IL-6 (b), RANTES (c), IL-15 (d) and TNFα (e) with a multiplex enzyme-linked immunosorbent assay. Data are from five mice per group±s.e.m. *P<0.05.

Mentions: To corroborate the RT-qPCR results, a Luminex enzyme-linked immunosorbent assay platform was used to measure the pro-inflammatory cytokines IL-6, IL-15, CCL2, RANTES and TNF in the BAL at day 8 pi (Figures 7a–e). The IL-15 protein level was significantly (P<0.05) increased when H7N9-infected mice were treated with Bindarit. Bindarit treatment did not appreciably change the level of other pro-inflammatory cytokines. Bindarit oral treatment also had minimal effect on cytokine expression levels in the lungs. Interestingly, CCL2 protein level was not reduced, but appeared enhanced after treatment with Bindarit.


Targeting the pro-inflammatory factor CCL2 (MCP-1) with Bindarit for influenza A (H7N9) treatment
Effect of Bindarit on protein level of pro-inflammatory following avian IAV H7N9 infection. Mice were infected i.n. with a sub-lethal dose of A/Anhui (H7N9) or PBS. Mice were then treated with either Bindarit or vehicle starting at day 1 pi. On day 8 pi, mice were killed and BAL was collected for protein expression analysis of CCL2 (a), IL-6 (b), RANTES (c), IL-15 (d) and TNFα (e) with a multiplex enzyme-linked immunosorbent assay. Data are from five mice per group±s.e.m. *P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig7: Effect of Bindarit on protein level of pro-inflammatory following avian IAV H7N9 infection. Mice were infected i.n. with a sub-lethal dose of A/Anhui (H7N9) or PBS. Mice were then treated with either Bindarit or vehicle starting at day 1 pi. On day 8 pi, mice were killed and BAL was collected for protein expression analysis of CCL2 (a), IL-6 (b), RANTES (c), IL-15 (d) and TNFα (e) with a multiplex enzyme-linked immunosorbent assay. Data are from five mice per group±s.e.m. *P<0.05.
Mentions: To corroborate the RT-qPCR results, a Luminex enzyme-linked immunosorbent assay platform was used to measure the pro-inflammatory cytokines IL-6, IL-15, CCL2, RANTES and TNF in the BAL at day 8 pi (Figures 7a–e). The IL-15 protein level was significantly (P<0.05) increased when H7N9-infected mice were treated with Bindarit. Bindarit treatment did not appreciably change the level of other pro-inflammatory cytokines. Bindarit oral treatment also had minimal effect on cytokine expression levels in the lungs. Interestingly, CCL2 protein level was not reduced, but appeared enhanced after treatment with Bindarit.

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.


Related in: MedlinePlus