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MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG‐E8, and induces polarization via TLR4‐dependent pathway
Author(s) -
Li Kangxin,
Chen Guiming,
Luo Haihua,
Li Jianhang,
Liu Aihua,
Yang Chen,
Wang Juan,
Xu Jia,
Gao Shenghan,
Chen Peng,
Jiang Yong
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29944
Subject(s) - efferocytosis , microbiology and biotechnology , macrophage polarization , rage (emotion) , tlr4 , inflammation , gas6 , cancer research , receptor , biology , signal transduction , macrophage , immunology , receptor tyrosine kinase , biochemistry , in vitro , neuroscience
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 κB 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.