PMID- 33128793 OWN - NLM STAT- MEDLINE DCOM- 20210907 LR - 20210907 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 236 IP - 2 DP - 2021 Feb TI - MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG-E8, and induces polarization via TLR4-dependent pathway. PG - 1375-1390 LID - 10.1002/jcp.29944 [doi] AB - 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 kappaB 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. CI - (c) 2020 Wiley Periodicals LLC. FAU - Li, Kangxin AU - Li K AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Chen, Guiming AU - Chen G AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Luo, Haihua AU - Luo H AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Li, Jianhang AU - Li J AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Liu, Aihua AU - Liu A AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Yang, Chen AU - Yang C AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Wang, Juan AU - Wang J AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Xu, Jia AU - Xu J AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Gao, Shenghan AU - Gao S AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Chen, Peng AU - Chen P AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. FAU - Jiang, Yong AU - Jiang Y AUID- ORCID: 0000-0002-8087-5717 AD - Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200720 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Ager protein, mouse) RN - 0 (Antigens, Surface) RN - 0 (Calgranulin A) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Mfge8 protein, mouse) RN - 0 (Milk Proteins) RN - 0 (NF-kappa B) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (growth arrest-specific protein 6) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Antigens, Surface/*genetics MH - Apoptosis/genetics MH - Calgranulin A/*genetics MH - Cell Polarity/genetics MH - Humans MH - Inflammation/*genetics/metabolism/pathology MH - Intercellular Signaling Peptides and Proteins/*genetics MH - Macrophages/metabolism/pathology MH - Mice MH - Milk Proteins/*genetics MH - NF-kappa B/genetics MH - Phagocytosis/genetics MH - Receptor for Advanced Glycation End Products/genetics MH - Signal Transduction MH - Thymocytes/metabolism/pathology MH - Toll-Like Receptor 4/*genetics MH - p38 Mitogen-Activated Protein Kinases/genetics OTO - NOTNLM OT - Toll-like receptor 4 OT - efferocytosis OT - myeloid-related protein OT - polarization OT - receptor of advanced glycation end products EDAT- 2020/11/01 06:00 MHDA- 2021/09/08 06:00 CRDT- 2020/10/31 17:08 PHST- 2020/01/12 00:00 [received] PHST- 2020/05/25 00:00 [revised] PHST- 2020/07/01 00:00 [accepted] PHST- 2020/11/01 06:00 [pubmed] PHST- 2021/09/08 06:00 [medline] PHST- 2020/10/31 17:08 [entrez] AID - 10.1002/jcp.29944 [doi] PST - ppublish SO - J Cell Physiol. 2021 Feb;236(2):1375-1390. doi: 10.1002/jcp.29944. Epub 2020 Jul 20.