Triphenyl phosphate-induced macrophages dysfunction by activation TLR4-mediated ERK/NF-κB pathway

Area of Science:

• Environmental Toxicology
• Immunology
• Molecular Biology

Background:

• Triphenyl phosphate (TPHP) is a widely used flame retardant found globally.
• Previous research linked TPHP to obesity, neurotoxicity, and reproductive issues, but its immune system effects remain largely unexplored.

Purpose of the Study:

• To investigate the immunotoxicity of TPHP on macrophages.
• To elucidate the underlying molecular mechanisms of TPHP-induced immune effects.

Main Methods:

• RAW 264.7 macrophages were treated with varying concentrations of TPHP.
• Flow cytometry, RT-qPCR, and phagocytosis assays were employed.
• The role of Toll-like receptor 4 (TLR4) and its downstream signaling pathway (ERK/NF-κB) was assessed using a TLR4 inhibitor (TAK-242).

Main Results:

• TPHP exposure induced a specific macrophage phenotype (F4/80+ CD11c+) and increased inflammatory mediator and antigen-presenting gene expression.
• TPHP enhanced macrophage phagocytic activity.
• TPHP upregulated Toll-like receptor 4 (TLR4) and CD14 expression, activating the ERK/NF-κB pathway.
• Inhibition of TLR4 blocked TPHP-induced phenotypic changes and inflammatory responses.

Conclusions:

• TPHP induces macrophage dysfunction by activating the TLR4-mediated ERK/NF-κB signaling pathway.
• This mechanism highlights a potential pathway for TPHP's adverse health impacts.