Arsenite inhibits M2a polarization of macrophages through downregulation of peroxisome proliferator-activated receptor gamma

Arsenite (As+3) is a group one human carcinogen, which has been associated with many diseases. Previous studies indicated that As+3 could inhibit wound healing and repair. M2a cells are known as tissue remodeling macrophages, which play an important role in wound repair process. Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a key regulator of lipid and glucose metabolism, was found to mediate the IL-4-dependent M2a polarization of macrophages. In the present study, As+3 induced dose-dependent inhibition of M2a polarization starting from 0.1 mu M in THP-1-derived macrophages stimulated with 20 ng/mL IL-4. Increased lipid accumulation and decreased PPAR-gamma expression were also observed in As+3-treated M2a macrophages. Rosiglitazone (RSG), a potent PPAR-gamma agonist, alleviated the suppressions of PPAR-gamma and M2a polarization induced by 2 mu M As+3. Collectively, these results not only demonstrated that As+3 was able to inhibit polarization of M2a cells through PPAR-gamma suppression, but also indicated that PPAR-gamma could be utilized as a target for the prevention and treatment of As+3-induced immunotoxicity.

Automated summary

The study found that arsenite (As+3) inhibits M2a cell polarization by suppressing PPAR-gamma and leads to lipid accumulation. Rosiglitazone (RSG) can alleviate the inhibitory effects of As+3 on PPAR-gamma and M2a cell polarization.