tetano
Editor, Senior Moderator
PLoS One
. 2021 Jul 19;16(7):e0254632.
doi: 10.1371/journal.pone.0254632. eCollection 2021.
Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival
Juan A De La Cruz[SUP] 1 [/SUP], Thota Ganesh[SUP] 2 [/SUP], Becky A Diebold[SUP] 3 [/SUP], Weiping Cao[SUP] 1 [/SUP], Amelia Hofstetter[SUP] 1 [/SUP], Neetu Singh[SUP] 1 [/SUP], Amrita Kumar[SUP] 1 [/SUP], James McCoy[SUP] 3 [/SUP], Priya Ranjan[SUP] 1 [/SUP], Susan M E Smith[SUP] 3 [/SUP], Suryaprakash Sambhara[SUP] 1 [/SUP], J David Lambeth[SUP] 3 [/SUP], Shivaprakash Gangappa[SUP] 1 [/SUP]
Affiliations
Abstract
Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1β) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44.
. 2021 Jul 19;16(7):e0254632.
doi: 10.1371/journal.pone.0254632. eCollection 2021.
Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival
Juan A De La Cruz[SUP] 1 [/SUP], Thota Ganesh[SUP] 2 [/SUP], Becky A Diebold[SUP] 3 [/SUP], Weiping Cao[SUP] 1 [/SUP], Amelia Hofstetter[SUP] 1 [/SUP], Neetu Singh[SUP] 1 [/SUP], Amrita Kumar[SUP] 1 [/SUP], James McCoy[SUP] 3 [/SUP], Priya Ranjan[SUP] 1 [/SUP], Susan M E Smith[SUP] 3 [/SUP], Suryaprakash Sambhara[SUP] 1 [/SUP], J David Lambeth[SUP] 3 [/SUP], Shivaprakash Gangappa[SUP] 1 [/SUP]
Affiliations
- PMID: 34280220
- DOI: 10.1371/journal.pone.0254632
Abstract
Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1β) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44.