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TLR4 antagonist FP7 inhibits LPS-induced cytokine production and glycolytic reprogramming in dendritic cells, and protects mice from lethal influenza infection.


ABSTRACT: Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1?) by monocytes and DCs (IC50?

SUBMITTER: Perrin-Cocon L 

PROVIDER: S-EPMC5247753 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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TLR4 antagonist FP7 inhibits LPS-induced cytokine production and glycolytic reprogramming in dendritic cells, and protects mice from lethal influenza infection.

Perrin-Cocon Laure L   Aublin-Gex Anne A   Sestito Stefania E SE   Shirey Kari Ann KA   Patel Mira C MC   André Patrice P   Blanco Jorge C JC   Vogel Stefanie N SN   Peri Francesco F   Lotteau Vincent V  

Scientific reports 20170120


Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Ou  ...[more]

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