MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG-E8, and induces polarization via TLR4-dependent pathway

Authors：Li, Kangxin; Chen, Guiming; Luo, Haihua; Li, Jianhang; Liu, Aihua; Yang, Chen; Wang, Juan; Xu, Jia; Gao, Shenghan; Chen, Peng^*; Jiang, Yong^*

Source：Journal of Cellular Physiology, 2021, 236(2): 1375-1390.

DOI：10.1002/jcp.29944

• efferocytosis
• myeloid-related protein
• polarization
• receptor of advanced glycation end products
• Toll-like receptor 4

Myeloid-related protein 8/14 (MRP8/14) participates in various inflammatory responses, however, its effect on macrophage efferocytosis remains unclear. Here, we demonstrate that MRP8/14 significantly inhibits the efferocytosis of apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs), which later proves to be associated with the receptor for advanced glycation end products (RAGE) or for reducing the expression of growth arrest-specific protein 6 and milk fat globule epidermal growth factor 8, independent of RAGE. Furthermore, MRP8/14 promotes polarization of BMDMs from the M-2- to M-1-like phenotype by upregulating expression of M-1-related surface receptor proteins and signature M-1-marker genes and by downregulating signature M-2-marker gene expression, which depends on Toll-like receptor 4 and p38 mitogen-activated protein kinase/nuclear factor kappa B pathways. Thus, we report a significant inhibitory effect of MRP8/14 on macrophage efferocytosis and MRP8/14-mediated phenotypic polarization, which may be helpful in developing novel therapeutic strategies leading to inflammation resolution.

• Institution
  南方医科大学; y