Iron ion polarizes macrophages to M1 subtype through ROS-acetyl-P53
ZHOU Yun;YI Zhujun;QUE Keting;ZHANG Zhen;LIU Zuojin;Department of Hepatobiliary Surgery,the Second Affiliated Hospital of Chongqing Medical University;
Objective To investigate the mechanism of M1 macrophage polarization induced by iron ion. Methods Western-blotting, real-time PCR, flow cytometry, immunohistofluorescence assay and reactive oxygen species(ROS) probe(DCFH-DA) were used to verify the effect of iron ion on promoting macrophages to M1 subtype,the expression levels of p53 and acetyl-p53,and the level of ROS production.Polarization indexes(IL-1β, TNF-α, IL-10, TGF-β, CD86 and CD206) were detected following the treatment of reduced glutathione hormone(GSH) or p300/CBP acetyltransferase inhibitor(C646). Ten BALB/c nude mice were divided into 2 groups,iron treatment and control groups. Xenograft model were prepared by subcutaneous injection of H22 cells in BALB/c nude mice to observe the polarization of tumor associated macrophage(TAM) after iron treatment. Results Iron polarized macrophages(RAW 264. 7 cells) to M1 subtype following the increasing of ROS production and high expression of acetyl-p53. GSH reduced ROS and acetyl-p53 level(P 0. 05). C646 inhibited the acetylation of p53 and attenuated the polarization of M1(P 0. 05). Subcutaneous tumor tissue expressed high level of CD86 and low level of CD206 in high iron treatment group,and a higher level of ROS was observed in the high iron treatment group than control group. Conclusion Iron promotes macrophages to M1 subtype,which may be through inducing ROS production,enhancing the activity of p300/CBP acetyltransferase,and then improving acetylation of P53.