PBMC-mediated modulation of macrophage polarization in RAW264.7 cells through STAT1/STAT6 signaling cascades

作者：Wenbo Zhang, Zuxiang Chen, Zhen Liu, Xinyu Qian, Yanzhi Ge, Haiyan Zhang, Wenting Xu, Letian Shan, Dongbao Zhao · 发表于：International Immunopharmacology · 年份：2024 · DOI：10.1016/j.intimp.2024.112651 · 被引用次数：15 · 研究领域：Immune cells in cancer、Phagocytosis and Immune Regulation、Macrophage Migration Inhibitory Factor

Peripheral blood mononuclear cells (PBMC), sourced autologously, offer numerous advantages when procured: easier acquisition process, no in vitro amplification needed, decreased intervention and overall increased acceptability make PBMC an attractive candidate for cell therapy treatment. However, the exact mechanism by which PBMC treat diseases remains poorly understood. Immune imbalance is the pathological basis of many diseases, with macrophages playing a crucial role in this process. However, research on the role and mechanisms of PBMC in regulating macrophages remains scarce. This study employed an in vitro co-culture model of PBMC and RAW264.7 macrophages to explore the role and mechanisms of PBMC in regulating macrophages. The results showed that the co-culturing led to decreased expression of inflammatory cytokines and increased expression of anti-inflammatory cytokines in RAW264.7 or in the culture supernatant. Additionally, the pro-inflammatory, tissue matrix-degrading M1 macrophages decreased, while the anti-inflammatory, matrix-synthesizing, regenerative M2 macrophages increased in both RAW264.7 and monocytes within PBMC. Moreover, co-cultured macrophages exhibited a significantly decreased p-STAT1/STAT1 ratio, while the p-STAT6/STAT6 ratio significantly increased. This suggests that PBMC may inhibit M1 macrophage polarization by blocking STAT1 signaling cascades and may promote M2 macrophage polarization through the activation of STAT6 signaling cascades. Overall,...